Mammalian Endo Exam 2

Home > Preview

The flashcards below were created by user moli4167 on FreezingBlue Flashcards.


  1. Which thyroid hormone is most abundant? Which one is biologically active?
    • T4 or thyroxine is most abundant.
    • T3 or triiodothyrone most biologically active.
  2. What is the structural difference between T3 & T4?
    T4 has 4 iodine molecules whereas T3 only has 3.
  3. When is thyroid hormone important?
    During the peri-natal life along with the early neonatal period.
  4. Where are receptors for thyroid hormone found?
    Everywhere! Probably in all tissues in body at some time or another
  5. Where are the target tissues for thyroid hormone?
    • skeletal muscle
    • cardiac muscle
    • liver
    • gastrointestinal tissue
    • kidney
  6. What is a critical nutrient for thyroid synthesis?
    Iodine
  7. Why is iodine an issue on a global level?
    Iodine is a rare element, present in ocean water but unevenly distributed in soils of world land masses
  8. What are the signs of hyperthyroidism?
    • increased BMR
    • elevated cardiac output
    • elevated body temperature
    • inappropriate sweating
    • weight loss associated with muscle catabolism
  9. What are the signs of hypothyroidism?
    • reduced BMR
    • enlarged heart with reduced cardiac output
    • decreased body temperature (reduced sweating)
    • myexdemia (accumulation of fluids  protein under the skin)
  10. What is a thyroglobulin?
    Very large protein in follicular cells that has tyrosine residues & can be ionated
  11. Where are thyroglobulins located?
    inside of colloids (inside of cell)
  12. What is a colloid?
    homogenous granules that contain secretory products, primarily thyroglobulin
  13. How is iodine absorbed?
    • dietary absorbed by GIT (converted to inorganic iodide)
    • -transported by plasma proteins
    • -upake by thyroid via active transport
    • -TSH importan for iodide uptake
  14. What happens if you have a large increase in dietary iodine?
    causes uptake of I to be temporarily blocked
  15. How is thyroid hormone secreted?
    • TSH binding causes pinocytosis of Tg
    • -releases T3 & T4
    • binds to receptor on thyroid gland & increases synthesis via several different mechanisms
    • tyrosine molecules get pinocytosed & released to peripheral tissue
  16. What are the various mechanisms by which thyroid synthesis is increased?
    • increased blood flow (angiogenesis)
    • increased thyroglobulin synthesis
    • increased trapping mechanism for iodine
  17. How if feedback of thyroid hormone synthesis controlled?
    • increased T3/T4 levels shut down thyrotroph cells of pituitary
    • T3/T4 concentrations sensed by pituitary & regulates presence of TRH receptor
    • most direct feedback is to thyrotrophs of pituitary
  18. What happens when antibodies fom against TSH?
    • TSH antibodies can interact with TSH receptors, increasing T3/T4 synthesis = hyperthyroidism
    • TSH is bound by antibody, no interaction with receptor, lots of TSH being released but not used = hypothyroidism
  19. What is the difference in hyper/hypothyroidism in regards to the TRH receptor?
    • Hyper = downregulates TRH receptor & decreases sensitivity of gland
    • Hypo = upregulates TRH receptor & increases sensitivity of pituitary to increase release of TSH
  20. Feedback sensitivity  regulation of thyroid
    • sensitivity of TSH dependent on feedback mechanism at pituitary level
    • TRH receptors regulate
    • T3/T4 feedback & change TRH released from hypothalamus
    • feedback at pituitary level, sensitivity of pituitary glands to TRH is what changes
  21. How is most thyroid hormone in circulation found?
    Bound to proteins
  22. How much thyroid hormone is free in circulation?
    0.4%
  23. Is the free or bound form of thyroid hormone important for biological response?
    Free form is required for biological response
  24. What are the three types of thyroid binding proteins, & how much of each is found
    • thyroxine binding globulin (TBG) - 75%
    • throxine-binding prealbumin - 20%
    • albumin -5 - 10%
  25. Explain the difference between T4 & T3 with thyroid hormone metabolism?
    • T3 is 3 - 5X more biologically active
    • T3 has a small vascular pool with a high turnover & is found in higher concentrations in target tissues
    • T4 has a large vascular pool with a slow turnover
  26. What are the broad ways thyroid hormone affects biological actions?
    • cellular differentiation & development
    • mammary development
    • metabolic actions
  27. How does thyroid hormone affect cellular differentiaion & development?
    • TSH can be regulator of GH
    • GH secretion diminished in absence of thyroid hormones
    • thyroid hormones induce GH & IGF production (especially in cases of disease)
  28. What processes of normal feal & neonatal development is thyroid hormone necessary for?
    • neuronal proliferation & differentiation
    • myelinogenesis
    • neuronal outgrowh
    • synapse formation
  29. Why are neonates screened for thyroid?
    • is low, supplementation is required
    • fetal thyroid functional at ~11 weeks
    • fetus does not receive much T3 or T4 from mother
  30. How does thyroid hormone stimulate anabolic & catabolic pathways?
    • protein synthesis & degradation
    • fat synthesis & degradation (cholesterol synthesis & LDL receptors)
    • carbohydate metabolism (increases rate of absorption of glucose from GI, glycogen synthesis & degradation)
  31. How does thyroid hormone affect cardiovascular?
    • increased HR, myocardial contractility & cardiac output (increased stroke volume)
    • hyperthyroidism increases HR & stroke volume
    • hypothyroidism decreases HR & stroke volume
  32. How does diet affect thyroid hormone?
    • T3 is increased during short-term overfeeding
    • plasma T3 decreased during prolonged fasting
    • starvation diet = reduced calorie intake = decreased amount of thyroid hormone due to reducing amount of heat produced
  33. What are the sympathetic effects of thyroid hormone?
    increased beta-adreneric receptorsin heart muscle, skeletal muscle, adipose tissue & lymphocyte
  34. What effect does thyroid hormone have on the skeleton?
    increased bone turnover
  35. How does thyroid hormone affect the GI?
    stimulates gut motility
  36. What does an increase in beta-adrenergic receptors trigger?
    increases tissues ability to interact with those hormones
  37. What gives tissue specificity with the thyroid hormone receptor?
    there are 5 isoforms
  38. What kind of receptor is the thyroid hormone receptor?
    nuclear receptor that interacts with transcription factors
  39. What are examples of genes that are up-regulated by thyroid hormones?
    • rat GH
    • oxytocin
    • nerve growth factor (NGF)
    • myosin heavy chain (alpha)
    • myelin basic protein
    • PEP carboxy kinase
    • Ca ATPase
    • Na/K ATPase
    • cytochrome oxidase
    • HMG-CoA reductase
  40. What are examples of genes that are down-regulated by thyroid hormones?
    • human GH
    • TSH
    • EGF receptor
    • myosin heavy chain (beta)
  41. Does hyper or hypothyroidism cause a goiter?
    both
  42. Why does a goiter occur?
    increased TSH secretion - attempt to stimulate iodide-trapping mechanisms & intrathyroidal metabolism of iodine
  43. What is Graves' disease?
    excess thyroid hormones that cause autoimmune disorder
  44. What are signs of Graves' disease?
    • eyeball bulging due to accumulation of fluid & connective tissue substance
    • goiter & skin thickening
  45. What causes Graves' disease?
    development of TSH-antibodies that mimic action of TSH production; long acting thyroid stimulator
  46. What is myxedema?
    hypothyroidism
  47. What are the signs of myxedema?
    • accumulation of fluids in face & periphery
    • mental deficiency occurs often
  48. What causes myxedema?
    • loss of functional thyroid tissue (Hshimoto's disease)
    • biosynthetic defects in hormonogenesis (inherited, iodine deficiency, anti-thyroid agents)
    • TSH or TRH deficiency
    • peripheral resistance to thyroid hormones
  49. What can cause cretinism?
    Autoimmune thyroiditis with early onset
  50. What is the largest endocrine organ?
    the gut
  51. What is the primary reason GI hormones are needed?
    digestion & moving food along tract
  52. What are other functions of GI hormones?
    • cause release of enzymes which are necessary to breakdown food substances
    • stimulate secretion of acids and/or bicarbonate (ensure pH optimum for enzyme activity)
  53. What is the function of gut hormones?
    traditional hormone messengers & neurotransmitters
  54. What functions do gut hormones mediate?
    • release of ions, water & bicarbonate to optimize gut pH
    • release of enzymes for splitting food molecules
  55. What was the first hormone to be described?
    secretin
  56. How were gut hormones located?
    immunochemical techniques
  57. What are the major gut hormones?
    • CCK
    • gastrin
    • secretin
  58. What are the major pancreatic hormones?
    • polypeptide
    • somatostatin
  59. Which gut hormones are appetite regulators?
    • CCK
    • polypeptide
    • GLP-1
    • polypeptide Y (PPY)
    • ghrelin
  60. CCK
    • cholecystokinin
    • duodenum & jejunum
    • presence of peptides & FA causes gall bladder to release
    • stimulates GI motility
    • increases GI blood flow
  61. What effect does CCK have on the CNS?
    induction of satiety
  62. What are the effects of CCK?
    • gallbladder contraction
    • pancreatic enzyme secretion (pancreatic exocrine secretion)
    • gastrointestinal motility
  63. How is CCK produced?
    produced by endocrine cells in proximal intestine & by neurons in central & peripheral nervous system
  64. Gastrin
    • stomach hormone
    • food in the gut is primary stimulus of gastrin release
    • stimulates HCl & pepsinogen release
    • stimulates GI motility
    • increases GI blood flow
  65. What is the effect of gastrin?
    acid secretion
  66. What is the major endocrine effect of gastrin?
    stimulate acid secretion by gastric parietal cells
  67. How is gastrin inhibited?
    • acidification of gastric contents
    • somatostatin
  68. What does gastrin regulate?
    growth of gastric mucosa
  69. How is gastrin secreted?
    • release of HCl in response to distension of stomach & presence of nutrients causes gastrin to be released from histamine
    • produced by endocrine cells in gastric antrum
  70. What stimulates gastrin release?
    • partially digested peptides & AAs
    • vagus nerve stimulation
    • bombesin/GRP
  71. Secretin
    • duodenum & jejunum
    • 1st released from acid-chyme
    • exocrine causes pancreas to release bicarbonate & pH increases
    • inhibits GI motility
    • increases GI blood flow
  72. What is the function of secretin?
    Pancreatic exocrine secretion
  73. What other functions does secretin perform?
    • stimulates pepsin secretion for the breakdown of peptides
    • inhibits secretion of gastric acid
    • inhibits GI motiltiy
  74. What is the main endocrine effect of secretin?
    stimualates secretion of water & bicarbonate ions by exocrine pancreas
  75. Where is secretin secreted from?
    endocrine S cells in proximal intestine
  76. Polypeptide
  77. Somatostatin
    • inhibits GI endocrine secretion
    • inhibits GI motility
    • endocrin from pancreas
    • GHIH inhibits gastrin in stomachinhibits GI motility
  78. What are the functions of somatostatin?
    • affects all major functions including endocrine secretion & gut motility
    • inhibits insulin &/or glucagon secretion
    • inhibits gastrin secretion (& HCl)
  79. What kind of effects does somatostatin produce?
    exclusively inhibitory effects
  80. Where is somatostatin found?
    hypothalamus, GI tract, pancreas
  81. GLP-1
    • enteroglucagons
    • role in insulin regulation
    • ileum
  82. What are the tropic effects of islet development & growth by GLP-1?
    • induces differentiation of beta cells in vitro from stem cells
    • agonist (exenatide) used to treat type II diabetes
  83. What causes GLP-1 to be released?
    response to carbohydrates, fat in GI tract
  84. What is the function of GLP-1?
    • inhibits gastrin
    • stimulates liver glycogenolysis
    • stimualates pancreatic release/synthesis of insulin
    • incretin activity
    • satiation
  85. GLP-2
    • enteroglucagonsrole in insulin regulation
    • ileum
  86. How is GLP-2 secreted?
    co-secreted with GLP-1
  87. What is the function of PYY?
    satiation
  88. What is the function of GLP-2?
    • trophic effects on intestines
    • gastrointestinl motility & growth
  89. GIP
    • Gastrin-inhibiting peptide, aka glucose dependent insulintropic peptide
    • duodenum & jejunum
    • inhibits GI motility
  90. What causes GIP to be secreted?
    oral glucose & AAs
  91. Where is GIP produced?
    in proximal intestine
  92. What is the function of GIP?
    • inhibits gastric acid secretion
    • stimulates insulin secretion/synthesis
  93. Motilin
    • duodenum & jejunum
    • keeps gut moving when fasting
    • stimulates GI motility
  94. What causes a suppression of motilin release?
    presence of nutrients in SI
  95. What causes an increase of motilin secretion?
    fasting
  96. Neurotensin
    • stimulates GI motility
    • increased GI blood flow
  97. PPY
    • role in appetite regulation
    • enteroglucagon in ileum
    • endocrine from pancreas
  98. What is the function of pancreatic polypeptide
    • inhibits pancreatic exocrine secretion & bile secretion
    • inhibits gastric emptying; reduces food intake
    • gastric motility
    • satiation
  99. What is the function of ghrelin?
    • hunger
    • growth hormone relese
  100. Insulin
    endocrine from pancreas
  101. Glucagon
    • endocrine from pancreas
    • inhibits GI motiltiy
    • increases GI blood flow
  102. How does the pancreas function as an exocrine?
    Acinar cells are source of digestive enzymes; digestive enzymes reach small intestine through ducts
  103. How does the gall bladder aid in digestion?
    • reservoir for bile salts excreted from the liver
    • bile salts allow for emulsification of fats in the SI
  104. What hormones are released from the stomach?
    gastrin
  105. What hormones are released from the duodenum & jejunum?
    • CCK
    • secretin
    • GIP
    • motilin
  106. What hormones are released from the ileum?
    • GLP (1&2)
    • PPY
  107. What hormones are released from the pancreas?
    • insulin
    • glucagon
    • pancreatic polypeptide
    • somatostain
  108. What are the over-arching ways GI hormones cause biological actions?
    • exocrine secretions
    • motility
    • endocrine secretion
    • blood flow
  109. How do GI hormones affect exocrine secretions?
    regulate secretion & absorption of water, electrolytes, enzymes & mucus
  110. How do GI hormones affect endocrin secretion?
    • bombesin (GRP, stimulator) & somatostain (inhibitor)
    • inhibitory effects on gastrin release are mediated by an increase in somatostatin
  111. How do GI hormones affect motility?
    • stimulate (gastrin, CCK, motilin, bombesin (GRP), neurotensin)
    • inhibit (glucagon, VIP, GIP, secretin, somatostatin)
  112. What hormones increase GI blood flow?
    Gastrin, CCK, secretin, glucagon, VIP, substance P, neurotensin
  113. Stats on obesity
    • US - 97 million obese
    • 2 of 3 overweight
    • 1 of 3 obese
    • ~5% of US population is extremely obese
    • obesity has increased 3X in last 30 years
    • WHO classifies it as an epidemic
  114. Compare obesity & anorexia with energy levels
    • Obesity: high energy in, low energy out
    • Anorexia: low energy in, high energy out
  115. What hypothalamic structures are involved in food regulation?
    • Arcuate nucleus
    • paraventricular & ventromedial
    • lateral hypothalamic area
    • brainstem
  116. How is the arcuate nucleus involved with food regulation?
    • it is the feeding control center
    • integrates hormonal signals for energy homeostasis
    • circumventricular organ
  117. How is the paraventricular & ventromedial areas involved in food regulation?
    satiety centers
  118. How is the lateral hypothalamic area involved in food regulation?
    • glucose sensitive neurons
    • stimulate feeding in response to hypoglycemia
  119. What structure of the brainstem is important for food regulation?
    vagus nerve
  120. How is the brainstem involved in food regulation?
    important connections with taste centers & hypothalmus
  121. What kind of connection is between the hypothalamus & brainstem?
    reciprocal connection
  122. What is the NTS & what part of the hypothalmus does it connect with?
    • nucleus of tractus salitarius
    • high density of NPY (neuro-peptide Y) binding sites
    • NPY content in NTS varies with feeding
    • connects with PVN
  123. What do the afferents from the vagus do for the brainstem?
    • satiety signals
    • role in individual meal size
  124. What is the reward center?
    limbic structures that have reciprocal connections to hypothalamus
  125. Why is energy balance tightly regulated?
    • energy intake varies & body weight conserved
    • food intake (meal size & frequency) must be conserved
  126. What are the long-term signals of body energy reserve?
    • leptin
    • insulin
  127. What are the short-term signals of body energy reserve?
    • ghrelin
    • PYY (peptide YY)
    • PP (pancreatic polypeptide)
    • CCK (cholecystokinin)
    • Oxm (Oxyntomodulin)
    • GLP-1 (Glucagon-like peptide 1)
  128. What short-term signals are orexigenic?
    ghrelin
  129. What short-term signals are anorexigenic?
    • PYY
    • PP
    • CCK
    • Oxm
    • GLP-1
  130. What is the difference between orexigenic & anorexigenic?
    • Orexigenic tells you to eat (hunger signal)
    • Anorexigenic tells you to stop (satiety signals)
  131. What is the difference between anorexia & anorexia nervosa?
    • Anorexia is lack of appetite
    • Anorexia nervosa is a disease condition
  132. How does the hypothalamus signal (overview)?
    integrates signals from peripherystimulates (NPY & AgRP) or inhibits (CART & POMC)
  133. Summary of central pathways involved in appetite regulation
  134. Is NPY orexigenic or anorexigenic?
    orexigenic
  135. Where is ghrelin synthesized?
    stomach
  136. How is ghrelin affected by fasting?
    circulating levels upregulated by fasting
  137. What influences ghrelin levels?
    • gut nutrients (not just amount)
    • glucose load but not volume suppresses ghrelin
  138. Can you drink a lot of water to stimulate ghrelin?
    No, ghrelin is affected by gut nutrients, not just amount in stomach
  139. What are plasma levels of ghrelin like during fasting versus eating?
    Plasma levels are high in fasting & drop after eating
  140. Where does ghrelin bind to its receptor?
    NPY neuron
  141. Does exogenous infusion affect ghrelin?
    Yes, can increase feed intake by 28% but there is no difference in satiety
  142. What is the relationship between ghrelin & BMI?
    • inverse relationship
    • lower ghrelin levels in obese subjects
  143. What is Prader Willi syndrome?
    • when food intake does not suppress ghrelin
    • hyperphagia
    • extreme obesity
    • hypogonadism
    • short stature
    • mental retardation
  144. What is PYY?
    peptide in NPY family
  145. Where is PYY produced?
    distal gut (L cells in crypt)
  146. How does a peripheral administration of PYY affect food intake?
    causes marked inhibition of food intake
  147. What is PYY similar to?
    secretin
  148. How does chronic administration of PYY affect food intake & body weight?
    decreases both
  149. What happens as a result of hypothalamic explants of PYY?
    inhibits release of NPY & stimulates release of alpha-MSH
  150. Where does PYY bind?
    binds to Y2R receptor on NPY neurons
  151. When is PYY released?
    • shortly after food intake as a neural response to gut fill
    • released again when food reaches distal SI
  152. What food nutrients cause increased PYY release?
    carbohydrates & fats
  153. What is co-secreted with PYY from the L cells in the distal SI?
    GLP-1
  154. How does PYY affect gut motility?
    • decreases gut motility
    • leads to sensation of fullness & satiety
  155. How is PYY affected by obesity?
    obese people have lower basal fasting PYY & have smaller rise after eating
  156. Where is PP secreted from?
    pancreatic cells
  157. How are levels of PP affected by fasting?
    low levels during fasting
  158. How do levels of PP change with phases of digestion?
    increase through all phases of digestion
  159. How does an IV administration of PP affect food intake?
    decreases food intake by 22%
  160. How does PP affect gastric emptying, appetite, & energy expenditure?
    • decreases gastric emptying & appetite
    • increasing energy expenditure
  161. Where is Oxm produced?
    produced from cleavage of preproglucagon in gut & brain
  162. Where does Oxm act?
    acts on GLP-1 receptor
  163. How does IV administration of Oxm affect food intake?
    decreases food intake by 20%
  165. Describe the action of Oxm on the GLP-1 receptor
    • is a GLP-1 receptor antagonist that blocks oxm actions
    • binds with very weak affinity
  166. Where is GLP-1 produced?
    produced from preproglucagon in gut & brain
  167. What is the function of GLP-1?
    acts at pancreas to release insulin
  168. How does GLP-1 affect food intake?
    inhibits
  169. How does central administration of GLP-1 affect food intake & energy expenditure?
    • inhibits food intake
    • increases energy expenditure
  170. What affect does the GLP-1 receptor antagonist have on food intake?
    increases food intake
  171. What is the significance of GLP-1 antagonist?
    levels achieved post-meal have a small affect on appetite
  172. What affects to GLP-1 analogs have?
    • improve glycemic control
    • decrease body weight
  173. Where is CCK secreted from?
    duodenal cells in response to chyme
  174. What gut hormone was the first to show anorexigenic effects?
    CCK
  175. What food nutrients affect CCK secretion?
    fat & protein
  176. How does IV infusions affect meal size & hunger?
    reduces meal size & postprandial hunger
  177. Compare the effect of NPY & POMC on appetite?
    • NPY stimulates
    • POMC inhibits
  178. What kind of hormone is leptin?
    adipocyte hormone
  179. How are leptin levels & body fat related?
    levels are proportional
  180. How does leptin affect food intake?
    inhibits
  181. Where does leptin bind?
    binds to receptor in hypothalamus
  182. How does leptin binding affect NPY/AgRP & POMC?
    • inhibits NPY/AgRP
    • stimulates POMC
  183. Why is weight regain a problem with weight loss?
    weight loss starvation associated with low energy expenditure, hyperphagia, & low leptin levels
  184. Is leptin sensitive to meal ingestion?
    no, it is relatively insenstive
  185. Why does leptin mutation (knockout) cause hypogonadism?
    leptin has role in regulation of GnRH
  186. How is transport of leptin across the blood brain barrier affected?
    • starvation reduces transport
    • refeeding increases transport
    • ob = mutation in gene for leptin
    • db = mutation in gene for leptin receptor
    • leptin resistance & obesity may occur at level of BBB
    • obese individuals have much lower level of leptin in CSF than in serum
    • possible that triglycerides block transport
  189. Where is insulin produced?
    pancreatic beta cells
  190. What functions does insulin have a role in?
    • regulates energy balance
    • essential for adipose tissue formation
  191. How are insulin levels & body mass related?
    levels are proportional to body mass
  192. How is insulin & obesity/diabetes correlated?
    • obesity associated with insulin resistance
    • precedes development of diabetes
  193. How does central administration of insulin affect food intake & body weight?
    decreases
  194. How does insulin enter the brain?
    receptor-mediated process
  195. In the brain, is insulin an orexigenic or anorexigenic signal?
    anorexigenic
  196. What neurons are targets for insulin?
    NPY & POMC neurons
  197. Is NPY orexigenic or anorexigenic?
    orexigenic
  198. What factors increase NPY mRNA?
    • low leptin
    • hypoglycemia
    • hypoinsulinemia
    • negative energy balance
  199. How does central administration of NPY affect thermogenesis, food intake, & adipogenesis?
    • inhibits thermogenesis
    • increases food intake
    • promotes adipogenesis
  200. How many receptors does NPY have?
    5 (Y1, Y2, Y3, Y4, Y5)
  201. Which NPY receptors mediate appetite effects?
    Y1, Y2 & Y5
  202. What evidence suggests that we are hunters/gatherers?
    • NPY was necessary to stimulate foraging behavior
    • anorexics have increased movement pathology & high NPY
  203. What is the AgRP?
    • Agouti Related Peptide
    • agouti is a protein associated with hair follicles
  204. Where is AgRP found?
    in the arcuate nucleus
  205. What does AgRP antagonize/stimulate?
    • antagonizes MC-3 & MC-4 receptors (MSH receptors)
    • stimulates appetite
  206. Is AgRP orexigenic or anorexigenic?
    orexigenic
  207. What does CART stand for?
    cocain & ampethamine regulated transcript
  208. What does POMC stand for?
    Pre-opiod melanin
  209. Is CART orexigenic or anorexigenic?
    anorexigenic
  210. Is POMC orexigenic or anorexigenic?
    anorexigenic
  211. What is POMC a precursor to?
    alpha-MSH (also ACTH)
  212. What does POMC mutation result in?
    red hair, adrenal insufficiency, early onset obesity
  213. What receptors does POMC use?
    MC3R & MC4R receptors
  214. What are characteristic signs of obesity due to a mutated MC4R gene?
    severe obesity, hyperphagia, hyperinsulinemia, increased fat-free & linear growth
  215. What does a MC4R agonist & antagonist do?
    • agonist inhibits feeding
    • antagonist causes hyperphagia
  216. Where is CART found?
    co-localized with POMC neurons in the arcuate nucleus
  217. What does CART mediate?
    anorexigenic effects of leptin
  218. What mediates CART?
    GLP-1
  219. How does GLP-1 mediate CART?
    blockage of GLP-1 receptors inhibits CART-induced hypophagia
  220. How does leptin administration affect CART?
    increases CART in ob/ob mice
  221. Are endogenous opiods & cannabinoids orexigenic or anorexigenic?
    orexigenic
  222. What function do opiod peptides have on feeding?
    • provide palatability & rewarding aspects of feeding
    • not necessary for energy need
  223. Where are endocannabinoid receptors located?
    localized in brain (pleasure centers; limbic system) as well as hypothalamus, GIT & adipose tissue
  224. What does central administration of endocannabinoids do to feeding & weight gain?
    increases both with repeated administration
  226. What does prohormone convertase do?
    • converts POMC to ACTH
    • affects synthesis of alpha-MSH, leading to hyperphagia
  227. What is the most common disorder in early-onset obesity?
    melanocortin 4 receptor
  228. What has gastric bypass surgery been associated with?
    • increased PYY & GLP-1
    • improved satiety & improved insulin sensitivity
    • hormonal changes noted before weight loss
  229. adipose tissue
  230. adipose tissue
  232. What are the hormones found in adipose tissue?
    • leptin
    • adiponectin
    • steroid hormones
    • retinol binding protein
    • visfatin
    • resistin
    • pro-inflammatory cytokines
  233. What is the traditional role of the adipose tissue?
    passive organ that plays metabolic role in energy homeostasis
  234. In what form does adipose tissue store & release energy?
    • stores energy as triglycerides
    • releases energy as fatty acids
  235. How is adipose tissue an endocrine organ?
    synthesizes & secretes hormones & adipokines
  236. What obesity-related disorders does adipose tissue contribute to the development of?
    type-2 diabetes & cardiovascular disease
  237. What tissues does adipose tissue provide cross-talk for?
    endothelium, muscle, liver, pancreas, adrenal glands, central nervous system
  238. What are some examples of adipose secretion products?
    fatty acids, prostaglandins, steroids, proteins
  240. How is adipose mass determined?
    by adipocyte number & size
  241. What is the initial increase in volume of adipose mass referred to as?
    hypertrophy
  242. What happens when cells reach critical size?
    triggers differentiation of precursor cells into mature adipocytes (triggers stem cells)
  243. How does adipose cell size affect its function?
    • large cells are less sensitive to insulin & have a higher rate of lipolysis
    • large cells have increased leptin production
    • cell size gives difference in gene expression
  244. What is the link between macrophage accumulation in white adipose tissue & BMI?
    positively correlated with increased BMI
  245. What do macrophages in white adipose tissue do?
    increase secretion of pro-inflammatory cytokines from adipose tissue
  246. What are the precursor cells for adipose tissue?
    multipotent mesenchymal stem cells & preadipocytes
  247. What does a deficiency of leptin cause?
    severe obesity, insulin resistance, impaired thermogenesis
  248. Are the problems associated with a deficiency of leptin reversable?
    yes with leptin treatment
  249. What is potentially occuring with leptin resistance in obese humans?
    • defective transport (crossing BBB)
    • defects in leptin signalling (leptin resistance)
    • antibody to leptin
  250. What is adiponectin?
    a very large protein
  251. Where is adiponectiin expressed?
    • mature adipocytes
    • higher levels in subcutaneous fat
  252. Where is adiponectin resistance occurring?
    resistance is at the receptor & transport so you can't supplement & correct problem
  253. What family does adiponectin structurally belong to?
    collagen superfamily
  254. In patients with increased fat mass, are adiponectin serum levels higher or lower?
    lower
  255. What are the two receptors for adiponectin & where are each found?
    • AdipoR1
    • expressed in muscle, hypothalamus co-localized with leptin receptor
    • AdipoR2
    • expressed in liver, hypothalamus co-localized with leptin receptor
  256. What kind of receptor are the adiponectin receptors?
    7-transmembrane domains
  257. How is serum adiponectin levels affected by obesity, type-2 diabetes & cardiovascular disease?
    reduced serum levels
  258. How does adiponectin contribute to insulin sensitivity?
    • adiponectin binding to its receptor activates specific intracellular pathways
    • increased glucose uptake & fatty acid oxidation in muscle
    • increased fatty acid oxidation & decreased gluconeogenesis in liver
  259. How does adiponectin cause antiatherosclerotic effects?
    • downregulates expression of vascular adhesion molecules
    • inhibits endothelial NFkB
    • inhibits monocyte adhesion to vascular wall
  260. What is an important suppressor of inflammation?
    adiponectin
  261. What is RBP4?
    • Retinol binding protein 4
    • a specific circulating transport protein for retinol
  262. How does RBP4 play a part in insulin resistance?
    impairs signaling at the muscle
  263. How are RBP4 serum levels affected by obesity & insulin resistance?
    increased
  264. What aspects of the metabolic syndrome are increased RBP4 serum levels associated with?
    • inflammation
    • fatty liver disease
    • insulin resistance
  265. How does adipose tissue normally respond as a glucose sensor?
    • detects absence of glucose by GLUT4 & responds by secreting RBP4
    • RBP4 inhibits insulin signaling
  266. How does RBP4 inhibit insulin signaling?
    • decreases PI3 kinase in muscle
    • inhibits phosphorylation of insulin receptor substrate-1 in muscle
    • gluconeogenic enzymes are upregulated in liver
  267. What is resistin?
    peptide hormone
  268. Where is resistin produced?
    adipocytes in rodents & macrophages in humans
  269. How do resistin levels change with feeding & adiposity?
    increase with both
  270. What structure is resistin similar to?
    adiponectin
  271. In obese type-2 diabetics, is resistin increased or decreased?
    increased
  272. Hyperglycemia is a result of what?
    increased hepatic glucose production in response to infusion or over-expression of resistin
  273. What does reducing resistin levels protect against?
    obesity-induced hyperglycemia
  274. Where is visfatin produced?
    produced by macrophages in adipose
  275. During adipogenic differentiation, are visfatin levels upregulated or downregulated?
    upregulated
  276. Do visfatin plasma levels decrease or increase during obesity development?
    increase
  277. What effect does visfatin have don cultured cells?
    • insulin-mimetic effects
    • stimulates glucose uptake & triglyceride incorporation
    • rbVisfatin lowered plasma glucose in mice
    • binds to & activates insulin receptor
  278. What are the proinflammatory cytokines?
    • tumor necrosis factor alpha (TNFalpha)
    • transforming growth factor beta (TGFbeta)
    • interferon-y
    • interleukins - IL6
    • monocyte chemotactic protein
    • factors of the complement cascade
  279. How do circulating levels of proinflammatory cytokines change with obesity?
    increase with increased obesity
  280. What steroid hormones are important in adipose tissue?
    • P450 aromatase
    • 11beta-HSD1
  281. What does P450 aromatase do?
    • converts androstenedione to estrone
    • converts testosterone to estradiol
  282. What does 11beta-HSD1 do?
    converts cortisone to cortisol
  286. When & who first clinically described diabetes?
    Celsus, 10AD
  287. When & who first coined the term diabetes?
    Aretaeus, 20AD
  288. When & who associated diabetes with the pancreas?
    Cawley, 1788
  289. When & who discovered pancreatic islets?
    Langerhans, 1869
  290. When & who showed experimental diabetes after pancreatectomy in dogs?
    Von Mering & Minkowskie, 1889
  291. When & who discovered insulin?
    Banding & Best, 1921
  292. What does diabetes mellitus refer to?
    • disorder characterized by polyuria
    • sweet
  293. In diabetes mellitus, how are blood glucose concentrations?
    abnormally high
  294. What is the main difference between type I & type II diabetes?
    • type I is insulin-dependent
    • type II is non-insulin dependent
  295. What does diabetes contribute to?
    • leading cause of kidney failure, lower-limb amputation, & blindness among adults
    • major cause of heart disease & stroke
    • 7th leading cause of death
  296. How is the pancreas an endocrine gland?
    endocrine function in nests of pancreatic cells called islets of Langerhans, composed of several different cell types each secreting a separate hormone
  297. What kinds of cells are found in the islets of the pancreas, & what do each secrete?
    • Alpha cells - glucagon
    • beta cells - insulin
    • delta cells - somatostain
    • f cells - pancreatic polypeptide
  298. How is the pancreas an exocrine gland?
    pancreatic juice contains digestive enzymes
  299. How is the release of pancreatic juice controlled?
    • controlled by reflex mechanisms after a meal
    • controlled by gastrointestinal hormones secretin & CCK
  300. What are the target tissues for insulin secreted by the pancreas?
    • muscle
    • liver
    • fat
    • hypothalamus
  301. What is the target tissue for glucagon secreted by the pancreas?
    liver
  302. pancreatic beta cell
  303. pancreatic alpha & beta cells
  304. inside of liver cell
    • feeding potent stimulus for insulin release
    • exercise & fasting potent stimulants for glucagon secretion
  307. Is insulin anabolic or catobolic?
    anabolic - energy storage
  308. What does insulin stimulate?
    transport of glucose & amino acids into cells
  309. What does insulin convert?
    precursor forms into storage forms
  310. What are the storage forms insulin converts to?
    glycogen, protein, triglycerides
  311. What stimulates insulin release?
    elevated blood levels of glucose (mainly) but also fatty acids or amino acids
  312. What are insulin anticipatory signals?
    • GI tract motility & stimulation by the parasympathetic nerves
    • activation of insulin secretion by acetyl choline
    • presence of CHOs in intestine causes release of GIP, insulin secretagogue & GLP-1
  313. What is the general effect of insulin?
    • promotes storage of glucose, fatty acids, & inhibits breakdown of glycogen & triglycerides
    • blocks or reverses effects of other hormones
    • activates phosphatases that remove phosphate from enzymes resulting in deactivation of that enzyme
    • reverses phosphorylation induced by cAMP-dependent protein kinases
  314. How does insulin stimulate glucose uptake?
    recruits glucose transport protein of GLUT4 in liver & muscle
  315. What happens after insulin is bound?
    • insulin internalized & degraded
    • receptors are not degraded but are recycled back to membrane
    • action on cell to increase rate of glucose uptake
  316. What is the difference in seconds, minutes & hours of insulin binding?
    • seconds - binds receptor, Tyr-Kinase activity
    • minutes - hexose transport, altered enzyme activity, gene regulation, receptor internalization & down regulation
    • hours - induction of DNA, RNA, protein & lipid synthesis, cell growth, down regulation of insulin receptor
  317. Where is glucagon produced?
    alpha cells of pancreas
  318. What is the major action of glucagon?
    elevate blood glucose levels
  319. Is glucagon anabolic or catabolic?
    catabolic - stimulates liver glycogenolysis & inhibits glycolysis
  320. What aids glucagon in triggering glycogenolysis in muscles & lipolysis in adipocytes?
    epinephrine
  321. How do epinephrine & glucagon both act to increase cAMP?
    enzymes become phosphorylated & active in pathways
  322. How does cortisol complement glucagon?
    stimulates gluconeogenesis in liver
  323. What are the signs of uncontrolled diabetes?
    • increased glucose in blood
    • loss of glucose through the kidney
    • increased loss of water
    • increased thirst
  324. What are the long-term effects of diabetes?
    • retinopathy
    • neuropathy
    • nephropathy
    • fatty liver
  325. Compare & contrast type I & type II diabetes (5 points)
    • Insulin - type I has lack of insulin, type II beta cells do not produce sufficient insulin
    • Cause - type I caused by destruction of beta cells, type II caused by resistance of insulin receptor
    • Development - type I rapid onset, type II gradual development
    • Age - type I usually before 35 years & most often between 10 - 16 years, type II usually over 40 years
    • Statistics - type I 10% of all diabetics, type II 90% of all diabetics
  326. What are the age related characteristics that contribute to type II diabetes?
    • 50% of adults >65 have pre-diabetes
    • increased incidence of central obesity
    • oxidative stress & mitochondrial dysfunction
  327. What are the genetic backgroung related characteristics that contribute to type II diabetes?
    black americans & pima indians have increased risk over caucasians
  328. How does lipotoxicity contribute to type II diabetes?
    • persistently elevated FFA levels leads to systemic insulin resistance
    • adipose tissue dysfunctions contribute to elevated FFA
    • may contribute to inflammation
  329. How are FFA levels controlled?
    • controlled by insulin
    • increased FFA with fasting, decreased after meal
  330. What are reasons for development of type II diabetes?
    • age
    • genetic backgroun
    • lipotoxicity
    • endoplasmic reticulum stress
    • hypoxia
    • oxidative stress
    • inflammation
    • adipokines
    • hyperinsulinemia
    • hyperglycemia
    • resistin
  331. How does endoplasmic reticulum stress contribute to development of type II diabetes?
    • accumulation of unfolded proteins causes ER stress
    • glucose, viral infections, hypoxia & lipids inhibit protein folding
    • drugs which relieve ER stress improve insulin sensitivity in liver
  332. How does hypoxia contribute to development of type II diabetes?
    • obstructive sleep apnea associated with insulin resistance in obese
    • may contribute to inflammatory response
  333. How does oxidative stress contribute to development of type II diabetes?
    • reactive oxygen species (ROS) generated by mitochondria during oxidation of FA & glucose for ATP
    • oversupply of FA & glucose in obesity causes oxidative stress
    • exercise may increase ROS but improved insulin sensitivity
  334. How does inflammation contribute to development of type II diabetes?
    • chronic, low-grade inflammation associated with obesity
    • inflammation inhibits insulin signalling
    • reduction of lipid synthesis by decreased PPARy & increased FFA
    • muscle insulin sensitivity is not sensitive to inflammation
  335. How do adipokines contribute to development of type II diabetes?
    • leptin inhibitory for insulin synthesis & secretion but at high levels, leptin appears to be stimulatory
    • adiponectin decreases with increased obesity; adiponectin protected beta cells from apoptosis in face of elevated glucose
  336. How does hyperinsulinemia contribute to development of type II diabetes?
    • over production & decreased clearance
    • role of leptin
  337. How does hyperglycemia contribute to development of type II diabetes?
    • increased glucagon synthesis & release
    • proliferation of alpha cells
    • increased production of liver glucose
  338. How does resistin contribute to development of type II diabetes?
    • decreased insulin receptors in beta cells
    • cause insulin resistance in pancreatic islets
  340. The severity of obesity in childhood does what for adult females?
    increases the likelihood of obesity
  341. What are the stats for obese children?
    • 43% are obese as adults
    • 29% are overweight
    • 28% become normal weight

Card Set Information

Author:
 moli4167
ID:
 205443
Filename:
 Mammalian Endo Exam 2
Updated:
 2013-04-02 17:45:29
Tags:
Endocrinology mammalian hormones
Folders:

Description:
Thyroid hormones, gut hormones, appetite regulation
Show Answers:

What would you like to do?

Home > Flashcards > Print Preview