McCumbee - Endocrine Pancreas Flashcards
Endocrine cells account for less than 2% of the total pancreatic mass, are organized in discrete clusters called _________
Islets of langerhans
Beta cells in the islet of langerhans secrete __
Insulin
Alpha cells in the islet of langerhans secrete
Glucagon
Insulin is packaged into secretory granules as _______
Proinsulin
The secretory granules that carry proinsulin also contain prohormone-converting enzymes that cleave proinsulin into? ___- and ___
Insulin
C peptide
What is the half life of insulin (circulatory half life)
5-8 minutes
The ______ is the principal site of insulin degradation
Liver
Hormones released by the intestines during a meal that stimulate glucose-dependent insulin secretion
Incretins
What are the causes of insulin release during a meal? (X3)
Glucose
Amino acids (basic AA’s have most response)
Incretins
The principal incretins in humans are:
GLP-1
GIP
Thru what transport method is insulin eventually released from beta cells?
Exocytosis
Somatostatin _____ the Beta cell release of insulin
Inhibits
Exercise and stress inhibit insulin release. This effect Is mediated by sympathetic stim via _______ adrenergic receptors
Alpha2
This protein is part of the insulin signaling pathway and has many phosphorylatable tyrosines that are then able to be bound by various proteins with the SH2 domain, giving insulin a variety of functional capabilities
Insulin receptor substrate (IRS)
___________ terminate insulin signal transduction by dephosphorylating the insulin receptor, IRS proteins, and other proteins phosphorylated during signal transduction
Protein-tyrosine phosphatases
Signal intensity of insulin can be _______ by the phosphorylation of serine residues on the insulin receptors
Lessened
_____ is the most physiologically important stimulus for the release of glucagon
Hypoglycemia
The primary target of glucagon action is the _____
Liver
The period time during which the cell metabolism consists primarily of the nutrients of that meal
Absorptive state
Lasts about 4 hours
Explain the GLUT2 transporters role in glucose levels.
GLUT2 is a low-affinity glucose transporter that moves glucose into and out of hepatic cells by facilitated diffusion. Post meal, when glucose levels are high, it transports glucose into the hepatocytes for storage. When glucose levels in blood are low, it does not move glucose into the cell because of its low affinity When blood glucose levels are lower, and the hepatocytes are making glucose, the GLUT2 transporters take glucose out of the cell and move it to the bloodstream.
Insulin ______ glucokinase expression
Increases
Glucose entering the liver during the absorptive state does what?
It is converted to glucose-6-phosphate by glucokinase
By regulating key enzymes in the liver, insulin ____ (x6)
Promotes the storage of glucose as glycogen.
Promotes glycolysis
Inhibits glycogenolysis
Prevents release of glucose by keeping in G-6-P form.
Inhibits gluconeogenesis
Stimulates fatty acid synthesis during period of carb excess
Liver glycogen peaks ______ to ___ hours after a meal
4 to 6
What sort of enzymatic response will you get if you eat a meal that is high in protein content and low in carbohydrate content?
Pancreas releases glucagon and insulin
Insulin - because of AA’s in proteins
Glucagon - low glucose medium, prevents insulin induced hypo-glycemia by stimulating hepatic glycogenolysis and gluconeogenesis
Glucose uptake by skeletal muscle during absorptive state is regulated by?
Primarily insulin
Lesser extent by blood glucose concentration
What does insulin do to increase the glucose uptake by skeletal muscle in the absorptive state?
It stimulates the translocation of the GLUT4 transporter that are stored in the intracellular vesicles, increasing Vmax of transport.
Insulin has a profound _________ effect on basal and hormonal stimulated lypolysis in fat cells
Inhibitory
Insulin acts by inhibiting hormone sensitive lipase inside adipocytes
What does insulin do to increase transport of glucose to adipocytes?
Signals the translocation of the GLUT4 transporters
Insulin has a stimulatory effect on fatty acid synthesis by stimulating?
Synthesis of lipoprotein lipase which breaks TAG’s to FA’s and glycerol
(Has to be done to get them in cell. Once in, combined w/ glycerol 3 phosphate to form IC TAG’s)
Insulin has a profound inhibitory effect on basal and hormone stimulated lipolysis IN fat cells. Insulin acts by _______ hormone-sensitive lipase inside adipocytes.
Inhibiting
(Hormone sensitive lipase catalyzes breakdown of TAG’s in fat cells into FA’s and glycerol)
[epinephrine is most potent physiological stimulator of hormone-sensitive lipase activity]
In the liver, insulin _____ ketogenesis
Suppresses
Rate of ketogenesis increases as the rate of ______ increases
Rate of flux of FA into liver increases
Insulin suppresses hepatic ketogenesis by ? (X2)
- Blocking lipolysis (insulin is a very strong inhibitor of hormone-sensitive lipase)
- Inhibiting carinitine acyltransferase (transfers fatty acids to mitochondria)
The principal substrates for hepatic gluconeogenesis during a fast are: (x4)
AA’s and lactate (from skeletal muscle)
Lactate (from RBC’s)
Glycerol (from fat)
Cortisol ______ protein catabolism
Promotoes
Important aspect of gluconeogenesis
Insulin ______ protein catabolism
Inhibits
Growth hormone levels increase w/in first 24 hours of a fast. What are the two effects on metabolism GH has that helps w/ fast
Stimulation of lipolysis
Inhibition of glucose uptake by skeletal muscle and adipose tissue (send it to more important muscles)
Plasma glucose, FFA, and glycerol levels usually stimulate after about ___ days of a fast
3
____ hormone from the thyroid regulates basal metabolic rate and is dropped after a fast that lasts from days to weeks?
T3
There is a 15-20% drop in basal metabolic rate in this kind of fast and T3 levels drop by half
Glucose from blood enters brain thru?
Glucose transporters in the endothelial cells by facilitated diffusion
Ketones enter the brain via?
Monocarboxylate transporters (MTC)
Causes of hypoglycemia: (x6)
- Drugs that potentiate effects of insulin or interfere w/ gluconeogenesis
- Insulinomas
- Rapid gastric emptying in pt’s w/ grastrectomies
- Adrenal/pituitary insufficiency
- Liver dz
- Inborn errors of carbohydrate metabolism
Hormones releases in response to hypoglycemia
Counterregulatory hormones
What are some counterregulatory hormones (x4)
Glucagon
Epinephrine
GH
Cortisol
