Glucoregulatory hormones Flashcards
Glucose levels are usually very ….. …….. .
Closely controlled
Via what three mechanisms is glucose obtained?
Intestinal absorption, glycogenolysis(liver) and gluconeogenesis (liver and kidney)
Which tissues use glucose?
All tissues i.e. muscle, brain, adipose, RBCs, kidney
List the hormones that maintain glucose homeostasis
Insulin, glucagon, somatostatin, pancreatic polypeptide
Insulin can be thought of as…
a “storing” hormone - a hormone of fuel storage and anabolism
List the sequence of insulin synthesis
Preproinsulin, proinsulin (stored in granules), insulin in beta-pancreatic cells
How does insulin secretion occur? In response to what?
Exocytosis in response to increasing intracellular calcium
What blood level of glucose is required to stimulate increased insulin secretion?
Blood glucose levels >5mmol increase insulin secretion rapidly
List the stages via which a high blood glucose stimulates insulin secretion
Glucose -> glut-2->enters B cells -> increases ATP -> closes K+ channes -> depolarisation -> opens Ca2+ channels -> Ca2+ enters cells -> triggers exocytosis of insulin
Give six triggers for insulin secretion other than glucose
- Arginine/leucine and other amino acids
- cAMP (NB adrenalin lowers cAMP and therefore inhibits insulin release
- Glucagon and theophylline via cAMP
- Autonomic stimulation via acetyl chloride
- GI hormones
- Oral hypoglycaemic drugs (these close ATP sensitive K+ channels
List four gastrointestinal hormones that trigger insulin secretion
GIP, enteroglucagon, secretin, CCK
List the inhibitors of insulin secretion
Somatostatin, beta blockers, K+ depletion, thiazide diuretics (via negative feedback)
Why is the liver exposed to high levels of insulin?
Because it is secreted into the portal blood
What is the effect of insulin on adipose tissue?
Increased glucose entry, increased fatty acid synthesis, increased TG deposition, inhibition of lipoprotein lipase, increased K+ uptake
What is the effect of insulin on muscle?
Increased glucose entry, increased amino acid uptake, increased protein synthesis, increased protein catabolism
What is the effect of insulin on the liver?
Decreased ketogenesis, increased protein synthesis, increased lipid synthesis, decreased glucose output
What is the effect of insulin in general?
Cell growth, stimulates whole body glucose uptake (skeletal muscle, heart muscle, smooth muscle and adipose tissue)
Which tissues do not respond to insulin?
Brain, liver, kidney, gut, RBCs, pancreatic B cells
What are the consequences of insulin deficiency?
Diabetes mellitus (decreased glucose uptake into peripheral cells and increased plasma glucose)
Increased rate at which amino acids are catabolised
Protein deficiency
Poor resistance to infections
Ketosis ->acidosis -> coma
How may glucagon be thought of?
A “mobilising” hormone
Give the sequence of glucagon synthesis. Where does this occur?
Preproglucagon -> glucagon. Occurs in the A-pancreatic islet cells.
Give the stimulants for glucagon secretion
Hypoglycaemia, aa, CCK, gastrin, cortisol, exercise, stress, infection, beta-adrenergic, theophylline
Give the inhibitors of glucagon secretion
Glucose (seems to require insulin), somatostatin, secretin, FFA, ketones, insulin, GABA, alpha stimulators
What are the cations of glucagon?
Primarily acts in the liver stimulating glycogen breakdown. In other tissues it stimulates lipolysis (adipose and liver). Inotropic to the heart, increases insulin secretion.
