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29 Cards in this Set
- Front
- Back
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Initial translation product of the human insulin gene:
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Preproinsulin
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What makes Preproinsulin into Proinsulin?
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Loss of the N-terminal signal peptide
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What makes Proinsulin into Insulin?
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Proteolytic cleavage at 2 sites to yield Insulin and C=peptide
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Where is insulin synthesized and processed?
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In the B-cells of the pancreas
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Where is it stored after synthesis and processing?
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In intracellular granules in the B-cells
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What are 2 things that stimulate B-cell secretion of Insulin?
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-Glucose (eaten)
-Sulfonylureas (drugs) |
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What are 3 things that inhibit B-cell secretion of insulin?
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-a-Adrenergic system
-Somatostatin -Calcium channel blockers |
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How do B-cells detect glucose levels?
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Glucose enters the B-cells via Glut2 transporters, gets metabolized, and raises the ATP/ADP ratio in the cells.
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What effect does increased ATP/ADP have in the B-cells?
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-Inhibits K efflux
-Depolarizes the cell -Calcium influx causes granule docking/exocytosis |
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Into what part of the circulation is insulin relesed?
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Portal circulation!
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What is the rate of release of insulin into the portal circulation in normal people?
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1 unit/hour
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What happens to half of the insulin secreted?
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Taken up and degraded by the LIVER (FPE)
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What happens to the other 1/2 of insulin that does reach systemic circulation?
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Rapidly degraded by muscle/kidney within 5 minutes
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What are 3 things that influence the overall 24-hr profile of insulin secretion in a typical person?
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-Basal secretion
-Nutrient stim'd secretion -Oscillations unrelated to meals |
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Why is the insulin in circulation so rapidly degraded by muscle/kidney?
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Because it is not protein bound
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What do you need to keep in mind when prescribing insulin?
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Check for renal disease and decrease the dose of insulin if they can't degrade as normal
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What are the 2 types of effects of insulin in general?
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-Anticatabolic
-Anabolic |
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What are the 3 tissue sites at which insulin exerts its effects?
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-Liver
-Adipose -Muscle |
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What are the 3 anticatabolic effects of Insulin at the liver?
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-Decreased Glycogenolysis
-Decreased gluconeogenesis -Decreased ketogenesis |
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Which is the most important anticatabolic effect of insulin at the liver?
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Prevention of gluconeogenesis
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What anticatabolic effect does insulin have on fat?
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Decreased lipolysis
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What 2 anticatabolic effects does insulin have on muscle?
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-Decreased Protein catabolism
-Decreased Amino Acid output |
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What are the 2 ANABOLIC effects of insulin at the liver?
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-Increased Glycogenesis
-Increased FA synthesis |
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What are the 3 ANABOLIC effects of insulin at ADIPOSE?
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-Increased glucose uptake
-Increased glycerol synthesis -Increased FA synthesis |
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What are 3 anabolic effects of insulin at MUSCLE?
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-Increased Glucose/AA uptake
-Increased Protein synthesis -Increased glycogen synthesis |
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What are the cellular mechanisms of insulin like in general?
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Pleiotropic
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What is the insulin receptor that mediates all of the pleiotropic effects?
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A plasma membrane tyrosine kinase receptor
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What happens when Insulin binds to the insulin receptor?
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Phosphorylation of insulin receptor substrates 1/2 (IRS)
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What follows the phosphorylation of IRS 1/2?
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Downstream effector molecules are activated (PDK and Ras)
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