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Glucagon _________ insulin; insulin ________ glucagon.
stimulates; inhibits
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Glucagon _________ somatostatin; somatostatin _________ glucagon.
stimulates; inhibits
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Juvenile onset of hypofunction of pancreatic islets is __________, characterized by... (2)
type I diabetes mellitus; lack of beta cells and insulin
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Type I DM is ________, making patients prone to _________.
insulin-dependent; ketosis
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Type I DM is initiated by a ___________ combined with _______ to... (3)
genetic predisposition; viral exposure; coxsackievirus, mumps, rubella (induces immune reaction against islets)
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Type I DM is seen in ________ (vetmed); it initially steams from __________ destruction of islets.
keeshond pups; immune-mediated lymphocytic inflammatory
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Inherited DM in Keeshonds exhibits __________ inheritance; clinical signs include... (5)
autosomal recessive; stunted growth, hyperglycemia, hypercholesterolemia, hypoinsulinemia, normal blood glucagon
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Why does Type I DM lead to stunted growth in keeshond pups?
hypoinsulinemia causes decreased protein anabolism and decreased AA uptake by muscle cells
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Type II DM is ________; insulin conc is ________ and blood glucose is _________.
insulin-independent; normal to increased; increased
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Describe the condition of pre-diabetes.
increased insulin, normal blood glucose; beta cells are hyperfunctioning trying to overcome insulin resistance
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Type II DM is characterized by _________.
insulin resistance
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______ (species) are very prone to type II DM.
Cats
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Horses often have pre-diabetes/metabolic syndrome associated with ________.
PPID
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What is the primary mechanism of insulin resistance with type II DM? What are its repercussions in the patient? (3)
down-regulation of insulin receptors; obesity, cortisol/GH excess, damage to pancreas
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When is accelerated insulin degradation a major source of insulin resistance?
gestational diabetes
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What is unique about rat islets?
rat islets can proliferate beta cells, leading to higher production of insulin--> makes rats less susceptible to Type II DM
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What is the current theory on betatropin gene function?
stimulates insulin secretion and beta cell hyperplasia in rats
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What is the progression to type II DM?
insulin resistance--> beta cells make more insulin to overcome--> stress on beta cells--> death/atrophy of beta cells
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How has the degeneration of islets been described in diabetic cats?
early on, islets swell; then, islets become vacuolated, vacuoles contain glycogen; finally, glycogen degeneration of the islets
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What processes play a role in islets atrophy in type II DM? (3)
degeneration of islet cells, inflammation, macrophages
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In cats, ________ may predispose them to type II DM.
amyloidosis
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Amyloidosis is a(n) _________ lesion in cats.
age-related
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What is the most common islet lesion in cats with clinical diabetes?
amyloidosis
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Amylin lowers _________ and increases _________.
glycogen synthesis; hepatic glucose output
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Type III DM involves _________ of islets due to... (5)
destruction; [chronic] chronic pancreatitis or cancer of exocrine pancreas, [acute] pancreatitis with hemorrhage and necrosis
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Chronic relapsing pancreatitis ultimately leads to... (4)
necrosis, fibrosis, atrophy, type III DM
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What are secondary lesions associated with DM? (5)
weight loss, cystitis, skin infections, liver cirrhosis, cataracts
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Describe cataracts associated with DM. (3)
bilateral opacity of lens, asteroidal, diffuse
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Diabetic hepatomegaly occurs because lack of insulin leads to __(2)__; also, there is toxic injury due to ___________.
lipolysis, increased mobilization of fat; hyperketonemia
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What are the 2 components of cirrhosis of the liver due to DM?
fibrosis and regenerative hyperplasia
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Cirrhosis of the liver is a sequelae to __________.
chronic fatty liver necrosis
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Pancreatic endocrine tumors are usually _________, ie. _________.
beta cell adenoma; functional insulinoma
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Insulinoma may result in the following functional disturbances... (2)
convulsive seizures due to hypoglycemia (exercise or fasting), favorable response to exogenous glucose
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Pancreatic endocrine tumors occur most commonly in... (3)
dogs, ferrets, cattle
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Pancreatic endocrine tumors are usually _________ carcinomas with a __________ that may take years to develop.
well-differentiated; high incidence of metastasis
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Clinical signs of insulinoma in ferrets. (6)
weight loss, pytalism, muscle tremors, hind limb weakness, hypoglycemia, hyperinsulinemia
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In ferrets insulinoma has a ______ of metastasis and a high incidence of...
low; recurrence in the pancreas after excision.
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Insulinoma in cattle is often found at slaughter as distant metastases in the _______ and ________.
regional lymph nodes; liver
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You see white nodules in the pancreas of an aged cat upon necropsy/exploratory surgery. What's going on?
exocrine nodular hyperplasia- common aging change, ESP in cats- NOT NEOPLASIA
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DM is a relative or absolute _____________, resulting in... (3)
insulin deficiency; chronic hyperglycemia, abnormal fat/protein metabolism, and damage to various organs.
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DM etiology has a spectrum from __________ to __________.
pure insulin resistance; complete lack of insulin production
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In order to diagnose DM, hyperglycemia must be documented __________ and best must be done to rule out _________ in cats.
consistently; stress hyperglycemia
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What are the consequences of hyperglycemia? (4)
glucose toxicity, cataracts, peripheral neuropathy, PU/PD
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PU/PD with DM is caused by ___________.
osmotic diuresis
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Inability of peripheral tissues to use glucose leads to reliance on ________ and _________ as energy sources.
FFAs; ketones
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Insulin deficiency leads to ________ in adipose tissue, _______ of fat, and _________. This leads to an immediate increase in serum __(2)__ and _________.
lipolysis; breakdown; weight loss; FFA and cholesterol; fatty liver
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Insulin deficiency leads to decreased ____________, leading to muscle breakdown and __________.
protein anabolism; weight loss
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How does insulin deficiency lead to polyphagia?
satiety center in the brain has insulin dependent mediated uptake of glucose
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A decrease in the insulin:glucagon ratio in the liver leads to increased __________.
ketone production
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Clinical signs/hallmarks of insulin deficiency. (4)
polyuria, polydipsia, polyphagia, weight loss
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Diabetic _____ WILL develop cataracts; diabetic ______ usually do not.
dogs; cats
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75% of diabetic dogs will develop cataracts within _______ of diagnosis.
1 year
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Glucose enters the lens freely; in a normal individual, it's used for energy; in a diabetic, the ________ is saturated, and glucose is metabolized through the _________ to __(2)__.
glycolytic pathway; polyol pathway; fructose and sorbitol
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__(2)__ are not freely permeable in the lens and lead to _________ of lens fibers and _______.
Fructose and sorbitol; swelling/rupture; cataracts
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Diabetic peripheral neuropathy is common in ________; it often presents as _________ with ___________.
diabetic cats; plantigrade posture; hocks touching the ground
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Etiologies of DM. (4)
inherited beta cell aplasia, beta cell destruction (drugs, viruses, pancreatitis, autoimmune), beta cell dysfunction, insulin resistance
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Type I DM results from _________ and loss of_________; there is often a _________; breed predisposition is ___________; ___________ breed are at low risk.
autoimmune destruction; beta cells; genetic predisposition; terriers/small dogs; large breed/boxers
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Diabetic dogs are usually classified as __________ because most dogs are _______ at diagnosis.
Type I DM; insulin-dependent DM
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In dogs, there is frequently an associated with DM and __________, which is _________.
pancreatitis; Type III DM
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Type II DM is characterized by __________ and __________.
beta cell dysfunction; insulin resistance
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Type II DM has a strong association with ________.
visceral obesity
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Risk factors for type II DM include __(2)__.
decreased physical activity, genetics
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Onset of Type II DM is usually ________ in life.
mid to late
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Amyloid deposition occurs in ________ and affects beta cells by ________.
cats and people; damaging them
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The proinsulin:insulin ratio is _________ in Type II DM and is an early marker of _________.
increased; beta cell dysfunction
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Decreased proinsulin conversion to insulin may predispose to ____________.
amyloid deposition
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In type II DM, insulin secretion is always at least ________ and in late disease is _________.
relatively decreased (relative to hyperglycemia); absolutely decreased
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A key feature of type II DM, there is decreased sensitivity of _______ to _______ and defects in the _________, leading to decreased __(2)__.
beta cells; glucose; incretin effect; GIP and GLP-1
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Glucose toxicity results from ___________; it causes... (4)
chronic persistent hyperglycemia; impaired insulin secretion, down-reguation of glucose transport, beta cell injury/death, overt diabetes
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What populations of cats are at greater risk for type II DM? (6)
male, neutered, obesity, old age, decreased physical activity, glucocorticoid and progestin administration
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Most cats are first presented as ________.
insulin-dependent DM
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Insulin deficiency is present but it is typically not an _________, rather ___________.
absolute deficiency; relative to the degree of insulin resistance
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In healthy individuals, insulin resistance results in...
compensatory response and increased capacity to secrete insulin.
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In diabetic individuals, insulin resistance leads to...
an abnormality in beta cells that does not allow an appropriate compensatory response.
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Insulin resistance occurs when a given concentration of insulin produces...
less biologic response than normal.
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Physiologic causes of insulin resistance. (5)
circulating insulin antagonists (counterregulatory hormones, cytokines), target tissue defects (receptor defects)
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Lifestyle causes of insulin resistance. (3)
obesity, inflammation, stress
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Results of insulin resistance in the liver. (1)
increased glucose output
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Results of insulin resistance in muscles/fat. (1)
decreases glucose uptake
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Results of insulin resistance in the pancreas. (4)
increased beta cell mass, increased insulin resistance, increased stress on beta cells, damage/death of beta cells
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If the pancreatic response to insulin resistance is normal, it results in _______ and ________ [insulin].
euglycemia; increased
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If the pancreatic response to insulin resistance is abnormal, it results in _________ and ________ [insulin].
hyperglycemia; slightly increased-low
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More obscure causes of DM. (4)
endocrinopathy, drugs, gestation, pancreatitis
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