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What enzyme degrades insulin? And in what organ?
- Insulinase will degrade insulin & it is found in the Liver
TRUE or FALSE: Insulin mobilizes FATTY ACIDS?
Insulin (stimulates/blocks) lipolysis?
- BLOCKS (via activation of cAMP PDE)
Glucagon (activates/inhibits) ketogenesis?
- Glucagon (activates/inhibits) ketogenesis
What kind of receptor is the insulin receptor?
- Tyrosine Kinase
What is the mechanism of glucose-stimulated insulin secretion, starting from the influx of glucose into the beta cells?
- Influx of glucose in beta islet cells --> ATP production inside cells (glycolysis) --> Blocking of ATP-sensitive K channel --> membrane depolarization --> Ca influx --> vesicle fusion --> insulin secretion!
What glucose transporter is REQUIRED by pancreatic beta cells to induce glucose-stimulated insulin secretion? Does this transporter have a low or high affinity for glucose?
- GLUT2 transporter, which brings glucose into the beta islet cells so it can release insulin
Insulin secretion occurs following _______ influx
- Ca (calcium) influx (allowing fusion of secretory vesicles)
Insulin is synthesized as ___________, which is then converted into ________ by the removal of the _________ sequence in the _______ _________ (organ). It is finally converted into insulin following cleavage of the ___-_________ inside the _________ (organ).
- Insulin is synthesized as PREPROINSULIN, which is then converted into PROINSULIN by the removal of the SIGNAL SEQUENCE in the ENDOPLASMIC RETICULUM. It is finally converted into insulin following cleave of the C-PEPTIDE inside the GOLGI.
What is the basic structure of insulin?
- Alpha-beta dimer held together by two disulfide bonds
What can help manage Type 2 Diabetes?
the Drug: Metformin
What causes Diabetes Mellitus?
Caused by a deficiency of insulin or a decreased response to insulin in target tissues
Type 2 Diabetes
--> Also known as Adult Diabetes
--> Onset frequently after age of 35 and symptoms develop gradually-
- - Cause: Obesity (almost/usually present)
- - Genetic predisposition
- - Effect: Insulin resistance combined with inability Beta cells to produce appropriate quantities of insulin
- - Acute complication: Hyperosmolar Coma
- - RESPONSIVE to treatment with oral hypoglycemic drugs
- - Treatment: Diet, exercise, oral hypoglycemic drugs, +/- insulin
Type 1 Diabetes
--> Also know as Juvenille Diabetes
- -->Onset usually during childhood or puberty and symptoms develop rapidly
- - Genetic predisposition: Yes
- - Effects: destroys Beta cells, no production of insulin
- - Complications: ketoacidosis
- - Treatment: needs to have constant supply of Insulin
Which GLUT receptor does insulin activate?
- Glut 4
What is used to distinguish insulin from exogenous injection for diabetic treatment?
Through what receptor does glucose enter the Liver?
What mechanism of action is glucagon under?
- Secondary messanger mechanism with cAMP and adenylyl cyclase
What increases glucagon secretion?
- Low blood glucose, Amino acids moved to glycolysis, epinephrine
What is the metabolic effect of glucagon on carbohydrate metabolism?
- IV admin of glucagon shows and immediate rise in blood glucose due to degradation of liver glycogen and increase in gluconeogenesis
What are positive inducers of glucagon?
- Epinephrine and Amino Acids
What is a negative inducer of glucagon?
- Glucose and Insulin
What cells secrete glucagon?
- Alpha cells of the islets of langerhans.
What do high levels of insulin promote?
- Degradation of receptors as a type of down-regulation
How are the actions of insulin terminated?
- Dephosphorylation of the receptor
What is the fourth point of insulin action? (final signal transduction)
- Phosphorylated IRS promotes activation of other protein kinases and phophatases, leading to biologic actions of insulin
What is the third point of insulin action? (third part of signal transduction)
- Receptor tyrosine kinase phosphorylates other proteins, for example, insulin receptor substrates
What is the second point of insulin action? (second part of signal transduction)
- Tyrosine residues of the beta subunit are autophosphorylated
What is the first point of insulin action? (first part of signal transduction)
- Insulin binding activates the receptor tyrosine kinase activity in the intracellular domain of the beta-subunit of the insulin receptor
What are positive inducers of insulin?
- Glucose and Amino Acids
What is a negative inducer of insulin?
What is the effect of epinephrine on fuel metabolism? where does it come from? and what is it controlled by?
- Rapid metabolism which is released by the adrenal medulla and controlled by the nervous system.
When is insulin secretion decreased?
- In times of stress, food scarcity, trauma or intense exercise.
What factors stimulate beta cells and insulin production?
- - Glucose
- - Amino Acids
- - Gastro Intestinal Tract hormones
What is insulin secretion coordinated with?
- The release of glucagon by pancreatic alpha cells.
Where is proinsulin formed?
- In the cisternal space
Where does the formation of preproinsulin occur?
- In the lumen of the R.E.R
Where is insulin stored and how is it released from storage?
- Stored in granules in the cytosol and are released by exocytosis.
What are the precursors of insulin?
- Preproinsulin and proinsulin
Which cells in the pancreas have glucokinase activity?
Beta cells in the Islets of Langerhans
What synthesis does insulin favor?
- Synthesis of glycogen, triaclglycerol and protein
From what cells is insulin produced?
- Beta-cells of the islets of langerhans in the pancreas.
What two hormones play a supporting role in fuel metabolism?
- - Epinephrine
- - Norepinephrine
What two hormones control energy metabolism?
What are the 4 organs which dominate fuel for metabolism?
- -Adipose tissue