Physiology-Endocrine Pancreas Flashcards
Which hormones ensure that we don’t become hypoglycemic?
Short term: Glucagon, NE & EPI. Long term: Cortisol & GH
Cells of the islet of Langerhans, what do they produce?
Alpha: glucagon, Beta: insulin, Delta: somatostatin
How do the alpha and beta cells sense and maintain insulin: glucagon balance?
1) Nutritional regulation: glucose & amino acid sensing. 2) Neural regulation: ANS (sympathetic from celiac ganglion and parasympathetic from vagus) 3) Hormonal regulation: catecholamines and gut hormones
How does glucagon:insulin ratio change during exercise?
Prior to exercise there is sympathetic activation of the islet and catecholamines begin to circulate. As exercise begins there is a drop in blood glucose. All of these things increase glucagon release and glucose production by the liver. Note the brain continues to take 6g/hr, but muscle’s glucose channels increase in response to exercise and decreased insulin, increasing glucose consumption 10x.
How does glucagon:insulin ration change after a carbohydrate meal?
Parasympathetic nervous system is dominant when eating, gastrointestinal hormones are released and blood sugar increases, favoring increased insulin release and glucose is shuttles into liver, fat and muscle for storage and energy.
Where does insulin route most of the glucose from meals?
50% liver, 25% peripheral uptake (brain, nerves, RBCs and testes) and 15% in fat and muscle (insulin-dependent tissues)
Where do we store most of our fuel stores?
1) Fat (141,000 kCal) #2) Muscle (600 kCal) #3) Liver (300kCal)
What does somatostatin do?
Inhibits GH and thyrotropin release. It is also inhibitory on alpha and beta cells of the pancreas (note that the pituitary is so far that the somatostatin that inhibits the pituitary does not affect the pancreatic cells at all)
Why would a somatostatin analogue specific for alpha cells be beneficial in treating type I diabetes?
Autoimmune destruction of the beta cell decreases insulin levels. The alpha cell is also insulin dependent in that it needs to be able to take glucose in in order to sense hyperglycemia. With low insulin, it can’t take glucose in and “senses” hypoglycemia and goes crazy secreting glucagon. If you could inhibit this it would preserve the little function there is left of the beta cells.
Why does proinsulin have a connecting peptide in addition to the active hormone? How is this useful for diagnostic purposes?
It is necessary for lining up the alpha and beta chains so the proper disulfide bridges could form that make the protein active. It is useful because active insulin is make by cleaving the c-peptide. If someone is making themselves sick by injecting insulin, they will not have an elevated c-peptide because it is not a natural hypoglycemia.
How is insulin a growth factor?
It “marshals” amino acid and glucose (GLUT4) receptors to the cell membrane surface. It also activates intracellular machinery for glucose utilization and storage. Ultimately signaling will reach the nucleus and promote cell growth and division.
Why is insulin’s receptor special?
Binding of insulin causes it to autophosphorylate and begin the cascade of phosphorylation of other intracellular enzymes.
What are the individual cells’ roles in controlling insulin response?
The can up regulate or down regulate insulin receptors, making them more or less sensitive to the effects of insulin. (spare receptors)
What people do we see insulin resistance in?
Obesity, mature-onset diabetes, GH excess, glucocorticoid excess and lipoatrophic diabetes.
What people do we see insulin sensitivity in?
Athletes (exercise marshals GLUT-4 receptors to cell surface stimulating increased uptake) and glucocorticoid insufficiency
How do glucocorticoids affect blood glucose levels?
Cortisol causes resorption of the insulin receptor, decreasing the amount of glucose taken up by the cells.
What does the liver need insulin for?
Not uptake of glucose, it does that on its own. It needs it for initiation of glycogen synthase to converts Glucose to Gluc-6-P
Actions of insulin on blood glucose homeostasis
Increase glucose uptake, increase glycogen synthesis, decrease glycogenolysis, decrease gluconeogenesis
Action of glucagon on blood glucose homeostasis
Increase glycogenolysis and gluconeogenesis
Actions of NE and EPI on blood glucose homeostasis
LIVER & MUSCLE: increase glycogenolysis, inhibit muscle uptake of glucose, increase muscle ability to utilize ketoacids as fuel and stimulation of gluconeogenesis in liver. ADIPOCYTES: inhibit lipogenesis and activate lipolysis by stimulating hormone sensitive lipases. PANCREAS: stimulate glucagon secretion and inhibit insulin release.
Actions of cortisol on blood glucose homeostasis
Increase gluconeogenesis and decrease glucose uptake by down regulation of insulin receptors. Promote lipolysis.
Actions of GH on blood glucose homeostasis
Decrease glucose uptake by down regulation of insulin receptors. Promote lipolysis.
What is the primary determinant of insulin secretion?
Nutritional regulation (glucose & AAs = secretion; hypoglycemia & hypoaminoacidemia = inhibit secretion)
Hormonal stimulators of insulin secretion? Glucagon secretion?
Insulin = GIP, secretin and gastrin. Glucagon = catecholamines.
3 precipitating events that can cause insulin-dependent diabetes in a susceptible child
Genetic predisposition, beta cytotrophic virus (Coxsackie) and chemical toxins can lead to formation of islet cell antibody.
What circle will eventually precipitate insulin-independent diabetes?
Excessive food intake + inadequate exercise -> obesity -> insulin resistance -> compensatory hyperinsulinemia. Eventually the beta cells burn out and causes diabetes. Further burnout will present with hyperglycemia, glycosuria and ketonemia indicating progression to insulin-dependent diabetes.
When do you see lack of c-peptide in people not taking exogenous insulin?
When beta cells are fully burnt out…usually after a stress response that increases counter regulatory hormones and induces severe ketoacidosis.
Why is obesity a significant contributor to chronic, low-grade inflammation in diabetes?
Lipid store accumulation -> Increased distance O2 must diffuse to get to mitochondria -> Hypoxia -> Upregulation of cytokines and monocyte chemotactic protein-1 -> Macrophages arrive and secrete cytokines -> Inflammation & insulin resistance
Leading cause of blindness in US and Europe
Diabetic retinopathy
