organ systems: glucose regulation

this lecture focused on glucose metabolism: specifically, the interplay of insulin and glucagon secretion and their effect of glucose metabolism and storage in different organs and tissues. the pancreatic islets of langerhans secrete glucagon from alpha cells, insulin from beta cells, and somatostatin from delta cells. glucagon is secreted in response to low blood sugar and has a variety of effects which ultimately serve to raise blood glucose levels. in the liver, glycogenolysis is initiated, freeing glucose units from storage (see the biochem chapter on glycogen for more detail), gluconeogenesis creates glucose from non-carbon precursors such as amino acids. additionally, triacylglyceride stores are converted into fatty acids, which can be cleaved into ketone bodies, which are used as an alternative fuel source. glucagon is released in response to hypoglycemic (low blood sugar) conditions. other mechanisms are in place to raise blood sugar: sympathetic stimulation, cortisol, growth hormone. the symptoms from severe hypoglycemia are caused by these mechanisms; hunger by the hypothalamus and anxiety/tremors/sweating by sympathetic stimulation.

on the other hand, insulin is released in hyperglycemic conditions (high blood sugar) and facilitates uptake of glucose into cells. it accomplishes this by binding to receptors that translocate glucose transport proteins to surface of cell membranes, thereby allowing glucose to enter. there are 5 categories of glucose transport proteins, with different affinities for glucose and found in different locations of the body (see the carb digestion biochem chapter for some more physiology of the GLUT transporters): GLUT1 are found everywhere in the body and also present in placenta. GLUT2 transporters are in the pancreas, liver, kidney, and intestine. GLUT3 transporters are everywhere in the body. GLUT4 transporters are in muscle and adipose tissue and are the only insulin dependent glucose transporters. GLUT5 transporters are in the jejunum.

insulin has a variety of actions on organs and tissues; in the liver it initiates glycogen storage, fatty acid synthesis and subsequent triacylglyceride synthesis. in adipose tissue it stimulates uptake of glucose, triacylglyceride synthesis, and triacylglyceride release (through VLDL's). in muscle it stimulates uptake of glucose and amino acids and promotes glycogen storage from the excess glucose. insulin release is stimulated by a variety of factors- primarily high blood glucose levels, but also via parasympathetic stimulation, amino acids, growth hormone, and various GI hormones. insulin release is inhibited by catecholamines, somatostatin, and glucagon. note: glucagon and insulin reciprocally regulate each other- the release of one inhibits the release of the other. in addition, the release of somatostatin inhibits the release of both insulin and glucagon- preventing "rapid nutrient exhaustion".

diabetes type I is caused by an autoimmune destruction of pancreatic beta cells, resulting in low insulin levels and therefore low glucose metabolism and therefore a shift to ketone body metabolism. this also results in increased glucose levels in the urine, which can cause polyuria (excess urine volume), polydipsia (excess thirst), and polyphagia (excess hunger). type II diabetes is a resistance to insulin that is associated with high visceral fat deposits with high lipolytic activity (releasing fatty acids into the bloodstream) that are resistant to the anti-lipolytic properties of insulin. this can be induced by high free fatty acid, cortisol, or testesterone levels.

questions
glucagon...
1. what are the three types of cells in the pancreatic islets of langerhans and what do they secrete?
2. describe glucagon's effect on the liver.
3. what are the specific processes that occur that release glucose and ketones from the liver?
4. what is glucagon release from alpha cells stimulated by?
5. what is glucagon release from alpha cells inhibited by?
6. how does somatostatin "prevent rapid nutrient exhaustion"?
7. glucagon corrects...
8. what are the other ways that the body corrects for hypoglycemia?
9. what are the symptoms of severe hypoglycemia and what are they caused by?
10. what is reactive hypoglycemia and what is it caused by?

insulin...
11. describe the general function of insulin.
12. how does insulin facilitate the uptake of glucose into cells?
13. where are GLUT1-GLUT5 found?
14. which glucose transporter protein requires insulin?
15. describe insulin's action on muscle.
16. describe insulin's action on the liver.
17. describe insulin's action on adipose tissue.
18. what are some factors that facilitate release of insulin from the pancreas?
19. what are inhibitors of insulin release?

hormonal regulation...
20. describe the "reciprocal regulation" of insulin and glucagon.
21. describe the concept of a "basin of attraction" in regards to glucose regulation.

diabetes...
22. what is IDDM? what is it caused by?
23. what do high glucose levels in urine cause?
24. what is type II diabetes? what is it caused by and what does it result in?

answers
1. alpha cells secrete glucagon, beta cells secrete insulin, delta cells secrete glucagon.
2. increases glucose and ketone production and secretion.
3. glycogenolysis, gluconeogenesis, lipolysis, ketogenesis.
4. amino acids, decreased bloods sugar, CCK, VIP, catecholamines.
5. insulin/glucose, somatostatin.
6. by inhibiting both alpha and beta cell secretion of glucagon and insulin secretion.

7. hypoglycemia.
8. sympathetic stimulation, cortisol, growth hormone.
9. anxiety, tremors, sweating are caused by sympathetic action and hunger is caused by hypothalamus.
10. low blood sugar levels after a meal that results from excess release of insulin triggered by high content of high glycemic index carbohydrates (or insufficient protein).

11. to store metabolic fuels.
12. by binding to receptors which translocate glucose transporter proteins into the cell membrane.
13. GLUT1- ubiquitous, placenta, GLUT2- beta cell, liver, kidney, intestine, GLUT3- ubiquitous, GLUT4- muscle,adipose, GLUT5-jejunum.
14. GLUT4.
15. causes uptake of amino acids and sugar (and therefore promotes glycogen storage).
16. glycogen synthesis, fatty acid synthesis.
17. uptake of glucose and converion into fatty acids and glycerols, triglyceride synthesis, and uptake of fatty acids from blood lipoproteins.
18. high glucose levels, amino acids, parasympathetic stimulation (cephalic phase of pancreatic secretion), growth hormone, cortisol, GI hormones such as gastrin, secretin, CCK, GIP.
19. somatostatin, catecholamines.

20. insulin and glucagon inhibit each other's release from islet cells via paracrine actions.
21. the basin of attraction is the set of homeostatic variables which the body settles into over time; long term changes in hormone levels or autonomic activity can shift this basin of attraction to a new equilibrium point.

22. autoimmune destruction of pancreatic beta cells which results in low levels of insulin, and thus a shift from glucose metabolism to ketone body metabolism.
23. polyuria (excess urine volume), polydipsia (excess thirst), polyphagia (excess hunger)
24. type II diabetes is an insulin resistance that is caused by excess fatty acids, cortisol, or testosterone, which blocks insulin's anti-lipolytic effect on adipose tissue. can not be compensated by excess insulin secretion.