Insulin and Glucagon Flashcards
The absorptive phase of substrate metabolism
Absorptive: during a meal blood levels of glucose, fatty acids, and amino acids increase allowing increased glycolysis and synthesis (FAO, Catabolic processes are inhibited)
Carbohydrates from meal
glycolysis increases, glycogen storage in muscles, fatty acid long chains in liver for storage
Citrate and Acetyl CoA
are both activated during glycolysis, Citrate activated fatty acid synthesis
Citrate mechanism
converts acetyl-CoA into malonyl-CoA which inhibits CPT1
Amino acids in absorptive phase
stimulated to enter cells for repair and replacement; excess are converted to TAG in liver
Fatty acids in absorptive phase
Fatty acids –>(liver) TAG—> (mobilized) in blood –> capillary walls (LIPOPROTEIN LIPASE) cleaves TAG to fatty acids for transfer into adipose cell–> fatty acid (in adipose cell) esterifies with glycerol to from TAG
Obligatory users of glucose
brain, RBC, nerves, intestinal mucosa, and renal medulla
Obligatory users of glucose have
highly sensitive glucose receptors and can utilize glucose even at low levels (>60)
CNA impairment is glucose drops below
60mg/100ml
Post-absorptive phase
goal to maintain plasma glucose through glycogenolysis, gluconeogenesis, lipolysis, and protein breakdown
Post-absorptive carbohydrates and protein
initially = glycogenolysis
Glucose-6-phosphate
enzyme that releases glucose into the bloodstream (muscle and brain do NOT have this)
muscle lacks G-6-P
converts glucose to lactate and secretes lactate which will go to the liver (Cori cycle) to be converted to glucose
After glycogenolysis, what occurs to maintain glucose levels
gluconeogenesis (lactate, pyruvate, glycerol, and AA)
Randle Effect
b-oxidation FAO can inhibit glycogenolysis to promote usage of fat as fuel
Transporting fatty acids into the mitochondria requires
acyl-CoA exchange of CoA for carnitine by CPT1
Once in the mitochondria acyl-carnitife is converted back to
acyl-CoA by CPT2
Ketogenesis
adaptation to starvation; during fasting mobilization of free fatty acids can be converted to ketones for alternative energy substrates for brain and other tissues; insulin ensures that ketone concentrations do not get too high
Type I DM
ketoacidosis can occur because of their lack of insulin to keep the ketones in balance during times of fasting
Pancreas
Alpha cells- glucagon
beta- insulin
D cells- somatostatin
F cells- pancreatic polypeptide
Insulin synthesis
preproinsulin formed in the beta cells of islets of langerhans cleaved into insulin and C-peptide and packaged in secretory vesicle
GLUT2
glucose receptor on beta cells
High plasma glucose
enters beta cells (GLUT2), increase in ATP, inhibit in K ion channels OPEN, depolarization, increase intracellular Ca, exocytosis of insulin
Sulfonylureas
close K+ channels to cause depolarization and release of insulin
Diazoxide
open K channels to hyperpolarize cell and inhibit insulin release
adrenergic stimulation of alpha-2 receptors on beta cells
inhibits insulin secretion
Insulin biphasic pattern
initial insulin spike (due to pre-synthesized hormone) followed by slower rise in insulin
Glucose levels of _______ or less do not stimulate insulin
80
The only time insulin and glucagon are stimulated simultaneously is
after a HIGH PROTEIN, no carb meal
Somatostatin ________ insulin secretion
inhibits
GI hormones ________ insulin secretion
promote
Catecholamines (EPI and NE) ____________ insulin secretion
inhibit (this prevents hypoglycemia during exercise)
Insulin binding causes
autophosphorylation of tyrosine kinase receptor, cAMP, IP3, and DAG responses that causes activation of anabolic processes and inhibition of catabolic
Glucose-dependent tissues (brain, nerves, RBC, intestinal mucosa, and renal medulla)
glucose transporters independent of insulin and dependent on plasma glucose (Sensitive)
GLUT4
glucose transporters on all other tissues that are insulin dependent
IN adipose tissue insulin
increased lipoprotein lipase for the transfer of fatty acids into fat cell and increased fat synthesis
Insulin __________ lipoprotein lipase in muscle
inhibits; divert fatty acids to adipose for storage not to muscle for usage
Insulin’s effect on Na/K ATPase and K, PO, and Mg uptake
insulin causes uptake of K, PO, and Mg and ATP production for the cell to use these in synthesis of glycogen and protein
Insulin directly _________ glucagon
inhibits; direction of blood flow goes from beta cells to alpha, therefore glucagon releasing cells are exposed to the highest level of insulin
Metabolism of insulin
liver and kidney, half-life of 5-8 min
Glucagon synthesis
pancreatic alpha cells, precursor molecule, Ca-dependent release
Synaptotagmin-7 Ca-sensing protein
initiates the glucagon release
Glucagon mechanism
cAMP 2nd messenger
Glucagon mainly acts on
LIVER (only acts on uncle and fat when its VERY HIGH, such as in Type I DM)
Glucagon effects
stimulation of glycogenolysis, gluconeogenesis, may stimulate lipolysis (@ HIGH conc), beta-oxidation, ketogenesis, AA gluconeogenesis, preoteolysis (@ HIGH conc)
Stimuli that increase glucagon
low glucose, low fatty acids, high amino acids, high cortisol, catecholamines
Stimuli that decrease glucagon
insulin, somatostatin, low AA, high glucose, and high fatty acids
Metabolism of Glucagon
liver and kidney (same as insulin)
Hormones that act/stimulate glucagon (counter-regulatory hormones to insulin)
catecholamines (EPI), cortisol, and GH (work under conditions of stress/exercise)
First line of defense to hypoglycemia
decreased insulin, increased glucagon, and increased epinephrine
Diabetes and insulin-dependent tissues
inability to uptake glucose stimulates gluconeogenesis adding to the hyperglycemia already experienced
inability to uptake AA, leading to proteolysis and elevates excretion of N and (-) Nitrogen balance
Which diabetes (Type I or II) will have increased glucagon secretion?
Type 1: without insulin, glucagon will not be inhibited
Why doesn’t ketoacidosis occur in Type II DM
because the presence of insulin limits lipolysis and ketone production
CHronic acidosis as seen in ketoacidosis may lead to
HYPERKALEMIA: elevated plasma K because cells exchange/pick up H and release K which can lead to overall K DEFICIT as it is excreted
Metabolic Syndrome
abdominal obesity, diabetes type II, elevated TAG, decreased HDL, elevated LDL, HTN,
INsulin resistance
decreased receptors, decreased GLUT4 transporters, decreased intracellular mechanisms
Treatment of Type II diabetes
SULFONYLUREAS: stimulate insuline release from beta cells OR exogenous insulin shots
