Unit 6 - Insulin and Glucagon Flashcards
Metabolic reserves in 70 kg man
what is the most important storage in case of starvation/
plasma/ECF glucose: 20 grams; would last an hour
glycogen: 100 g in liver, 200 in muscle; would last part of a day
protein: 10-12 kg, mostly in skeletal muscle; about half is available for energy before death from starvation due to respiratory muscle failure
fat: 10 kg in adipose tissue; lasts ~40 days with water
- most important E reserve in case of starvation
at what level is plasma glucose regulated at? what regulates it? which are anabolic and catabolic?
80-100 mg/dL (4-5 mmol/L)
- down-regulated by insulin only (anabolic)
- up-regulated by glucagon, NE, E, cortisol, GI hormones (catabolic)
how much glucose and O2 does the brain use?
relies exclusively on circulating glucose to meet E needs
- consumes more than 20% of O2 supply
- stores little glycogen, and cannot oxidize FA or AA, but can use ketone bodies if starving
- vulnerable to hypoglycemia, quickly making coma and death
what do the following islet of Langerhans cells do:
- alpha cells
- beta cells
- delta cells
- F cells
a: glucagon made and secreted at periphery (25% of IoL)
b: insulin, proinsulin, and c-peptide made and secreted at center (60% of IoL)
d: somatostatin made and secreted, dispersed in periphery
F: pancreatic polypeptide (GI hormone) made and secreted, dispersed in periperhy
what does pancreatic polypeptide do?
inhibits GB contraction and pancreatic exocrine secretion
post-translational processing of glucagon
proglucagon processed differently in pancreas and intestine
- IoL alpha cells: becomes GRPP, glucagon, and major proglucagon fragment
- L cells: becomes glicentin, GLP-1/2, IP-2 (glucagon-like peptide and inhibitory peptide)
how is glucagon packaged, stored, and circulated?
packaged and stored in membrane bound granules, and secreted like other peptide hormones
- circulates unbound with half-life of 3-4 minutes
- degraded in liver (80%) and kidney, with little in urine
what are stimulators of glucagon secretion?
- hypoglycemia (<50 mg/dL blood glucose); most important
- increased arg and ala (indicates PRO degradation)
- exercise (liver supplies glucose to muscle)
- stress (during healing after surgery)
what are inhibitors of glucagon secretion?
- somatostatin (paracrine that inhibits release of insulin and glucagon, along with gastrin, gastric acid secretion, and all gut hormones)
- insulin (antagonist to glucagon)
- hyperglycemia (above 200 mg/dL); max inhibition
which organ has the most glucagon receptors?
liver
what are the effects of glucagon in the liver?
catabolic hormone that activates AC, increases cAMP, which activates PKA to phosphorylate key enzymes in glycolysis and gluconeogenesis
- increases glycogenolysis, gluconeogenesis, and lipolysis
- decreases glycolysis, glycogen synthesis, and lipid formation
what are counter-regulatory hormones?
glucagon, catecholamines, growth hormones, and cortisol
- released in times of stress (exercise, illness, etc.)
- keeps blood glucose levels high enough to support brain metabolism
proinsulin processing, storage, and secretion
packaged in Golgi, and processed during sorting to storage granules that contain endopeptidase with trypsin-like activity
- proinsulin and endopeptidase are secreted together with Zn to join the 6 insulin molecules into hexamers
- cleaved into insulin and C-peptide
what is the clinical use of C-peptide?
no known biological activity, but level in blood is used to quantitate endogenous insulin production in patients getting exogenous insulin
- this works because insulin is used by liver, muscles, and other organs, so you cannot measure it directly
- -since C-peptide isn’t used by anything, it is a good marker to see how much insulin was made
what is recombinant human insulin used for? crystalline zinc insulin?
rHI: avoid antibody reactions
CZnI: basic pharmaceutical preparation used to treat DM
insulin half life and degradation
half life of 5-8 minutes
-degraded by insulinase in liver, kidney, and other tissues
