Physio: Endocrine - Endocrine Pancreas
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- What hormone is secreted by the alpha cells of the islets of Langerhans?
- glucagon
- In what part of the islet are the alpha cells located?
- outer rim
- What hormone is secreted by the beta cells of the islets of Langerhans?
- insulin
- In what part of the islet are the beta cells located?
- center
- What hormone is secreted by the delta cells of the islets of Langerhans?
- somatostatin (and gastin)
- In what part of the islet are the delta cells located?
- intermixed
- What are 3 ways in which the cells communicate with each other?
-
1) gap jns (a-a, b-b, and a-b)
2) portal blood supply (venous blood from one cell type bathes other cell types)
3) via nervous innervation - What is the structure of proinsulin?
- A chain and B chain connected by C peptide
- What is the significance of the C peptide?
- it's conc is used to monitor beta cell fn in diabetic pts receiving exogenous insulin (b/c it's secreted along w/insulin)
- Describe the cellular mechanism of insulin secretion.
-
1. Gluc binds GLUT 2 on beta cell, moves into cell
2. Gluc is oxidized to ATP
3. ATP binds and closes K channel, cell depolarizes
4. Ca channels open, Ca rushes in
5. Stimulates insulin release - Which is a more powerful stimulant for insulin secretion: oral glucose or intravenous glucose? Why?
- oral; it stimulates s/c of gastric inhibitory peptide (GIP), which has independent stimulatory effect on insulin
- What class of drugs mimics the action of ATP in beta cells (closing K channels to depolarize the cell)?
- sulfonylurea drugs (e.g. tolbutamide, glyburide)
- For what condition are sulfonylurea drugs most commonly administered?
- type II (non-insulin dependent) diabetes mellitus
- What is the structure of the insulin receptor?
- 2 extracellular alpha subunits which connect 2 membrane spanning beta subunits with tyrosine kinase activity (autophosphorylation)
- Under what conditions does insulin up-regulate and down-regulate its own receptor? How?
- up-regulates during starvation, down-regulates during obesity (type II diabetes); it internalizes receptor after binding, and can inc or dec degradation/recycling
- What are the mechanisms by which insulin decreases blood glucose concentration?
-
1. directs insertion of glucose transporters in cell membranes
2. promotes formation of glycogen in musc & liver, and inhibits glycogenolysis
3. inhibits gluconeogenesis - By what biochemical mechanism does insulin inhibit gluconeogenesis?
- stimulates fructose 2,6-biphosphatase, which increases phosphofructokinase activity
- What are the mechanisms by which insulin decreases blood fatty acid and ketoacid concentration?
- stimulates fat deposition and inhibits lipolysis, which decreases amount of available acetyl CoA, which inhibits ketoacid formation
- What are the mechanisms by which insulin decreases blood amino acid concentration?
- stimulates AA uptake, increases protein synthesis, inhibits protein degradation
- What are the menchanisms by which insulin decreases blood K concentration?
- increases K uptake into cells by increasing activity of Na-K ATPase
- What is the overall effect on insulin on blood levels of glucose, amino acids, fatty acids, ketoacids, and potassium?
- decreased gluc, aa, fatty acids, ketoacids, and K
- What are some factors that stimulate insulin secretion?
- inc blood glucose, aa's, and fatty acid, glucagon, GIP, ACh, growth hormone, and cortisol (neg feedback?)
- What are some factors that inhibit insulin secretion?
- dec blood glucose, somatostatin, epinephrine, NE
- What symptoms would a patient with type I (insulin-dependent) diabetes mellitus present with?
- hyperglycemia, hyperkalemia, hypotension (gluc acts as osmotic diuretic), ketone breath, metabolic acidosis (from ketoacids), hyperventilation (respiratory compensation)
- What factors stimulate glucagon secretion?
- dec blood glucose, INCREASED AAs (esp arginine), CCK, NE, epin, ACh
- What factors decrease glucagon secretion?
- inc blood glucose, insulin, somatostatin, fatty acids, ketoacidds
- What are the major actions of glucagon?
- stimulates glycogenolysis and gluconeogenesis, inhibits glycogen formation, increases lipolysis and ketoacid formation
- What is the 2nd messanger mechanism of action for glucagon?
- cAMP
- What is the effect of somatostatin?
- inhibit secretion of both insulin and glucagon (modulatory effect)
- What stimulates secretion of somatostatin?
- ALL forms of nutrients, various GI hormones, glucagon, beta-adrenergic agonists (is inhibited by insulin)