Glucagon and Insulin Flashcards
1
Q
metabolic reserves in a 70kg man
A
- plasma/ECF glucose-20 g would last 1 hour
- glycogen-100g in liver, 200g in muscle, enough for part of one day
- protein- 10-12 kg, mostly in skeletal muscle, about 1/2 available for energy needs before death from starvation due to respiratory muscle failure
- fat-10kg mostly in adipose tissue- lasts 40 days with water
2
Q
blood glucose homeostasis
A
- insulin, glucagon, norepi, epi, cortisol, GI hormones, somatostatin
- blood glucose to brain, liver, heart, muscle, adipose tissue
- 80-100 mg/dl
- brain relies almost exclusively on circulating glucose to meet energy demands
- consumes more than 20% of oxygen supply
3
Q
islet of langerhans
A
- constitute approximately 1-2% of the mass of the pancreas
- highly vascularized and receives SNS and PNS inputs
- beta cells secrete insulin, 60% of islets
- alpha cells secrete glucagon from periphery of islets, 25%
- delta cells secrete somatostatin, in periphery
- F cells secrete pancreatic polypeptide, periphery- inhibits gallbladder contraction and pancreatic exocrine secretion
4
Q
post translational processing of glucagon
A
- GRPP, glucagon, glicentin, GLP1, IP2, GLP2
- glucagon most understood
- circulates unbound and has a half life of 3-4 min
- degraded in the liver and kidney, with little excreted in the urine
5
Q
glucagon 1
A
- 29 aa, MW 3500 D
- 160 aa pro-glucagon
- packaged and stored in membrane bound granules and secreted like other peptide hormones
6
Q
stimulators of glucagon secretion
A
- hypoglycemia (less than 50)- most important
- increase in arginine and alanine (indicative of protein degradation)
- exercise- liver supplies glucose to muscle
- stress- during healing after surgery
7
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
- hyperglycemia (above 200)
8
Q
effects of glucagon in liver
A
- binds to Gs and increases cAMP and PKA
- catabolic hormone
- glucagon rises during food deprivation
- mobilizes glycogen, fat, protein to increase blood glucose
- counter regulatory hormone released in times of stress
- glycogenolysis, gluconeogenesis, and increases lipolysis
9
Q
processing of pro-insulin
A
- proinsulin and endopeptidase (trypsin like) secreted together
- C-peptide has no known activity, but level in blood quantitates endogenous insulin production
- 51 aa with MW 6000D
- preproinsulin-proinsulin-golgi and processed to storage granules-proinsulin cleaved to C peptide
- used recombinant human insulin to prevent reactions today
- half life of 5-8 minutes, degraded by insulinase in the liver, kidney and other tissues
10
Q
control of insulin secretion
A
- glucose stimulates release of insulin
- if you perfuse pancreas, jump in insulin and then slow rise due to increased synthesis of insulin
11
Q
insulin secretion by beta cells
A
- glucose enters the cell via GLUT2 transporter
- increased glucose influx stimulates glucose metabolism, leading to an increase in ATP or ATP:ADP ratio
- the increased ATP inhibits ATP sensitive K channel
- Inhibition of K channel causes Vm to depolarize
- the depolarization activates a voltage gated Ca channel
- the channel causes Ca influx, which induces CICR
- elevated Ca leads to exocytosis and release of insulin
- insulin also increased by glucagon/B adrenergic agonists and Gs/ PKA
- galactose and mannose and certain aa can also stimulate fusion of vesicles
- CCK and Ach-stim Gq and PLC and PKC and therefore insulin
- inhibited by somatostatin/alpha-adrenergic by binding to Gq and decreasing cAMP and PKA
12
Q
why is insulin increased by glucagon
A
- glucagon signals starvation so we need increased blood glucose, but we want some insulin out so that protein degradation doesn’t happen in the muscles to become a source of glucose
- major target organ of glucagon is liver but insulin has a large effect on skeletal muscle
13
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 is plasma glucose is primary stimulus for insulin secretion
- incretins provide an advance notice of feeding and stimulate insulin secretion, oral glucose yields more insulin than IV does
- CCK and GIP enhance insulin
- GLP-1 similarly increases insulin during feeding
14
Q
stimulators of insulin secretion
A
- inc serum glucose, aa, free FA, ketone bodies
- GIP, glucagon, gastrin, CCK, secretin, VIP, epi (B-receptor)
- PNS
15
Q
inhibitors of insulin secretion
A
- dec glucose, aa, free FA
- somatostatin, epi via alpha
16
Q
response of catecholamines and insulin during exercise
A
- circulating epi stimulates insulin secretion via B receptor
- local autonomic stim via alpha dominates
- net result is to suppress insulin secretion and to precent hypoglycemia caused by excessive uptake of glucose by muscle
- reduced insulin also permits the liver to supply glucose to muscle, and adipose tissue to supply FA to muscle
17
Q
anabolic action of insulin on liver
A
- stimulates glucose uptake and decreases output
- stimulates formation of glycogen and inhibits glycogenolysis
- promotes glycolysis and lipogenesis
- decreases fat oxidation, gluconeogenesis, and ketogenesis
- promotes protein synthesis and inhibits protein breakdown and the urea cycle
- glu enters through non-insulin sensitized channel- just increase of glucose in blood
18
Q
anabolic action of insulin on muscle
A
- taken up by GLUT 4, which increases in the OM in response to insulin binding to a receptor
- promotes glycogenesis and glycolysis, aa uptake and protein synthesis and decreases proteolysis
19
Q
anabolic action of insulin on adipocyte
A
- glut 4 transporter again thats added in response to insulin receptor
- synthesize more fat
- increases glycolysis and a-glycerophosphate- inc esterification of fats
- decreases lipolysis
- stimulates lipoprotein lipase-moves to surface endo cells where it releases FA from chylomicrons and VLDLD to go back into the cell for lipid synthesis
20
Q
glucose tolerance test
A
-normal subject shows increase in insulin to response in glucose, diabetic does not
21
Q
diseases involving abnormal levels of insulin and glucagon
A
- insulin deficiency-type I diabetes
- insulinemia-elevated levels of insulin in blood
- glucagon deficiency very very rare
- glucagnoma-high levels of glucagon in blood-hyperglycemia
22
Q
control of appetite
A
- lateral hypothalamus
- NTS
- leptin, insulin, ghrelin, CCK, GLP1, PYY
23
Q
orixigenic factors
A
- nt that stimulate feeding
- neuropeptide Y
24
Q
anorexigenic factors
A
- nt that inhibit feeding
- corticotropin releasing hormone, GLP1, alpha MSG, cocaine
25
Q
satiation signals
A
- satiation signals secreted in response to food ingestion
- single meal time frame
- GI distension triggers vagal afferents that suppresses hunger center
- CCK, GLP1, glicentin, GLP2, glucagon, peptide tyrosine-tyrosine
- CCK diffuses locally in a paracrine fashion to stimulate CCK1 receptors on branches of vagal sensory nerves
- message that ingested fat and protein is being processes and will soon be absorbed is conveyed to the NTS and relayed to the hypothalamus
- ghrelin is secreted from oxyntic glands of stomach- only GI hormone to increase food intake-increase before meals and decrease after
- works with arcuate nucleus
26
Q
adiposity signals
A
- leptin and insulin-hormones secretion in proportion in the amount of fat in the body
- leptin from white adipocytes
- both hormones cross the blood brain barrier and gain access to the hypothalamus to influence energy homeostasis
- neurons sensitive to insulin and leptin receive a signal proportional to amt of fat in the body
- leptin and insulin stimulate proopopmelanocortin neurons to produce alpha melanocyte stimulating hormone, which binds on receptors on other hypothalamic neurons and elsewhere to reduce food intake
- leptin and insulin inhibit agouti-related peptide and NPY containing neurons in the ARC-similar projections as POMC
27
Q
meal onset
A
- controlled by social, cultural and environmental factors
- low leptin levels, hypoglycemia, hypoinsulinemia, and conditions of negative energy balance all enhance NPY/AgRP expression in ARC
- activate orexin and MCH expression to increase urge of food intake
-satiation signals activate vagus nerve and pass info to NTS
