Unit VI- Insulin and Glucagon Flashcards
1
Q
Metabolic reserves in 70kg man
A
- plasma/ecf glucose- 20g would last an hour
- glycogen- 100 g in liver; 200 in muscle- enough for part of one day
- protein- 10-12 kg, mostly skeletal muscle, about 1/2 available for energy needs before death from starvation due to respiratory muscle failure
- fat- 10 kg mostly in adipose tissue, lasts -40 days with water
2
Q
Blood Glucose Homeostasis
A
- plasma glucose- 80-100 mg/dl or 4-5 mM
- all of peripheral tissues use glucose to produce ATP for energy but the brain is particularly dependent on plasma glucose
- insulin, glucagon, catecholamines, and gastro-intestinal hormones regulate the homeostasis of plasma glucose
3
Q
Insulin
A
- synthesized by beta cells
- located in center of the Islets of Langerhans of the pancreas
- it is a anabolic hormone secreted in times of excess nutrient availability
- allows the body to utilize and store carbohydrates
4
Q
Glucagon
A
- a catabolic hormone secreted during times of food deprivation
- glucagon along with the catecholamines epi and norepi allows utilization of stored nutrient reserves by mobilizing glycogen, fat and protein to serve as energy sources
5
Q
Somatostatin
A
-a paracrine that inhibits the release of insulin and glucagon as well as gastrin, gastric acid secretion, and all gut hormones
6
Q
The Brain
A
- relies almost exclusively on circulating glucose to meet its energy demands
- it consumed more than 20 percent of oxygen supply
- brain stores little glycogen and cannot oxidize fatty acids although it can utilize ketone bodies
- vulnerable to hypoglycemia, which can quickly produce coma and death
7
Q
Islets of Langerhans
A
- normal pancreas 500,000 to several million islets, 1-2% of mass of pancreas
- each islet is highly vascularized and receives sympathetic and parasympathetic inputs
- insulin, proinsulin, and c-peptide secreted by beta cells (60%)in the center of islets
- glucagon synthesized and secreted by alpha cells (25%) at periphery
- somatostatin synthesized and secreted by delta cells dispersed in Islets’ periphery
- F cells- in periphery secrete pancreatic polypeptide a gastro-intestinal hormone: inhibits gallbladder contraction and inhibits pancreatic exocrine secretion
8
Q
Synthesis and degradation of Glucagon
A
- 29 amino acid peptide of molecular weight 3500D, but synthesized as 160 amino acid pre-groglucagon
- postranslation processing yields glucagon, glicentin (69 aa), glicentin-like peptide, glucagon-like peptide 1 and 2
- glucagon circulates in the blood unbound to carrier proteins and has a half-life of only 3 to 4 min
- glucagon is degraded in the liver (80% and the kidney with very little excreted in the urine
- packaged and secreted like other peptide hormones
9
Q
Stimulators of Glucagon Secretion
A
- Hypoglycemia (<50 mg/dl blood glucose)- most important
- increase in arginine and alanine-indicative of protein degradation
- exercise- liver supplies glucose to muscle
- stress- during healing after surgery
10
Q
Inhibitors of Glucagon Secretion
A
- somatostatin- paracrine that inhibits release of insulin and glucagon, as well as gastrin, gastric acid secretion, and all gut hormones
- insulin- antagonist to glucagon
- hyperglycemia- above 200 mg/dl -max inhibition
11
Q
Effects of Glucagon in Liver
A
- a catabolic hormone
- levels of glucagon rise during periods of food deprivation and consequently stored nutrient reserves are mobilized
- glucagon mobilized glycogen, fat and protein to increase blood glucose
- counter regulatory hormone that is released in times of stress to keep blood glucose high enough to support brain
- primary target is liver, where it antagonizes insulin
- stimulate glycogenolysis and gluconeogenesis
- increases lipolysis (breakdown trigylcerides into fatty acids and glycerol
12
Q
Processing of Proinsulin
A
- peptide comprised of two disulfide linked chains 51 amino acids, 6000D
- synthesized in preproinsulin
- proinsulin packaged in the golgi and is processed during sorting to storage granules which contain endopeptidase with trypsin-like activity, also have zinc which acts to join 6 insulin molecules into hexamers
- proinsulin is cleaved into insulin and C peptide
- C peptide is used to measure insulin production
- half life of 5-8 minutes, degraded by insulinase in liver, kidney and other tissues
- recombinant human insulin,crystalline zinx insulin
13
Q
Control of Insulin Secretion
A
- after ingestion of food, the fast component or early phase of insulin release occurs within 10 minutes of ingestion of food, and peaks about 30-45 mins
- after an IV dose of glucose the first peak is the release of stored insulin
- the peak falls in 10 mins, if stimulus maintained insulin release increases gradually for hour- late phase of insulin release proabably newly formed insulin
14
Q
Insulin Secretion by Beta Cells
A
- increased extracellular trigger the beta cell to secrete insulin
- glucose enters the cell via a GLUT2 transporter, which mediates facilitated diffusion of glucose into the cell
- the increased glucose influx stimulates glucose metabolism leading to an increase in ATP
- increased ATP inhibits ATP-sensitive K+ channel
- inhibition of this K channel causes Vm to become more positive (depolarization)
- voltage gated Ca2+ channel activated
- activation of Ca2+ channel promotes Ca2+ influx - Ca induced Ca release
- elevated Ca leads to exocytosis and release into the blood of insulin contained secretory granules
- galactose and mannose and certain amino acids can also stimulate fusion of vesicles that have pre synthesized insulin
15
Q
Response of Insulin after feeding
A
- Cephalic phase- gastric acid secretion and small rise in plasma insulin mediated by vagus nerve
- intestinal phase- glucose absorption and rise in plasma glucose is primary stimulus for insulin secretion
- incretins provide advance notice of feeding and stimulate insulin secretion: oral glucose yields more insulin than IV
- CCK and GIP enhance insulin secretion
- glucagon-like peptide similary increases insulin during feeding
