Zaczek RS 2- Insulin and Glucagon Flashcards
What is the process of insulin synthesis?
Preprohormone is synthesized on rough ER ribosomes.
The leader sequence on the polypeptide directs it into the ER, where it is processed into proinsulin by the cleavage of the leader sequence and folding to form the disulfide bonds
Proinsulin is shipped to the Golgi, where it is packaged into granules
In the granules, C-peptide is cleaved off and insulin polymerizes
What are the two blood supplies to the liver? How much nutrient and oxygen comes from each?
The hepatic artery and hepatic portal vein are the two blood supplies to the liver.
The hepatic portal is 70% nutrients, 30% wastes.
The hepatic artery is 30% nutrients and 70% wastes.
Which hexose transporters move glucose according to it’s concentration gradient? Which move it against?
GLUT Transporters (1-5) move hexoses according to it’s concentration gradient
SGLT transporters move glucose against their concentration gradient
What is the biochemical cascade of events leading to the exocytosis of insulin granules?
GLUT2 transporters are the beta cell glucose sensors of beta cells.
High glucose will cause more ATP to be produced.
ATP closes a constitutively open potassium channel, that is keeping the cell hyperpolarized.
The closing of this channel leads to depolarization, causing voltage gated calcium channels to open.
Calcium triggers a cascade of events that leads to cAMP formation and the release of insulin.
What are direct insulin secretagogues? Indirect
Direct: Hyperglycemia (most potent), parasympathetic stimulation, Amino acids, fatty acids, ketoacids (insulin is involved in their storage),cAMP, theophylline (inhibits cAMP degradation)
Indirect: Glucagon, beta-adrenergic activation (insulin is involved in the storage of their products)
How do sulfonylureas work? What are 3?
They close the ATP-dependent K+ channels, leading to insulin release
Tolbutamide, glipizide, glyburide
What are incretins? What are 4 of them?
Incretins are molecules that either directly or indirectly stimulate the release of insulin
Secretin (From S-cells), CCK (I-cells), GIP (K-cells), GLP-1 (L-cells)
What are some inhibitors of insulin secretion?
Hypoglycemia Somatostatin Potassium depletion Galanin (keeps the potassium channel on beta cells open) Alpha adrenergic innervation
How is glucagon synthesized? What is the difference in how it is processed in the two places?
Glucagon is synthesized as proglucagon in both the L-cells of the intestine and the alpha cells of the pancreas.
In the intestine, it is cleaved into the incretin GLP-1. In the pancreas, it is cleaved into glucagon.
What are the secretagogues of glucagon?
Protein meals, especially those rich in glucogenic amino acids.
Hypoglycemia and starvation (inhibit insulin, therefore disinhibit glucagon secretion)
GI Hormones: Gastrin and CCK
Beta adrenergic stimulation (stress, exercise and infection can all increase)
What are some inhibitors of glucagon secretion?
Hyperglycemia
Insulin and GABA (both stimulated by hyperglycemia)
GI hormones: Secretin
Somatostatin
Free fatty acids and ketones via negative feedback
Alpha-beta cell crosstalk
How can insulin and glucose be used to treat hyperkalemia and renal failure?
Insulin stimulates Na/K ATPase activity, so infusions of insulin and glucose, which may cause hypokalemia in normal patients, can be a temporary treatment of hyperkalemia in individuals with renal failure
