Duan-EBM Flashcards
Describe some of the organs that are involved in glucose homeostasis.
liver–glucagon causes glycogenolysis & glucose release
muscle–insulin causes glycogen synthesis
kidney–insulin causes increased absorption of glucose from filtrate
all tissues–insulin causes glucose to go into cells.
What is released from pancreatic beta cells?
insulin
C-peptide
amylin
What is released from pancreatic alpha cells?
glucagon
Proteolysis of proinsulin yields what?
insulin
C-peptide
4 basic AA
Describe the structure of insulin.
A & B chains (2)
joined by disulfide bonds & 1 intrachain bond
What is the biologically active form of insulin?
monomeric form
What’s the deal with human insulin preparations?
recombinant protein by genetic engineering.
What types of substances in food cause secretion of insulin?
glucose–really stimulates insulin
AA–like arginine & lysine
fatty acids, ketones
What type of nervous system things affect insulin release?
vagus nerve–M receptors–increases insulin release.
sympathetic activation–alpha receptor–>inhibits insulin release. beta 2 receptor–>activates insulin secretion.
What types of things will cause sympathetic nerve stimulation & regulation of insulin release?
exercise hypoxia hypothermia trauma burns
What does glucagon do to insulin release?
glucagon stimulates insulin secretion
What does insulin do to glucagon release?
insulin inhibits release of glucagon
T/F Injectable glucose stimulates more insulin release than eating glucose.
False. Eating causes more insulin release.
Describe how glucose transport into pancreatic beta cells leads to insulin release.
glucose transported into beta cell via GLUT2.
rate limiting step: phosphorylation of glucose via glucokinase.
Metabolism of glucose–>more ATP.
High ATP–>inhibition of ATP sensitive K+ channel. Membrane depolarization. Ca++ rushes in & you get fusion of insulin-containing secretory granules w/ plasma membrane & exocytosis of insulin.
Aside from glucose rushing in, what other substances help raise cAMP & cause exocytosis of insulin-containing granules?
GLP-1
incretins
acetylcholine (NT)
Describe how insulin is broken down?
mainly by the liver & kidney
insulin binds receptor on cell & forms a complex that is internalized.
Complex degraded via thiol metalloproteinase (hydrolyzes disulfide linkage b/w A & B chains).
Receptor recycled to plasma membrane.
What are the 3 main targets of insulin?
liver
muscle
adipose
What does insulin do to the liver?
decreases gluconeogenesis & glycogenolysis
increases glucose uptake & glycolysis
increases triglyceride synthesis
increases protein synthesis
What does insulin do to muscles?
increases glucose uptake & glycolysis
increases glycogen synthesis
increases protein synthesis.
What does insulin do to adipose tissue?
increases glucose uptake & glycolysis
decreases intracellular lipolysis
increases lipogenesis & lipoprotein lipase activity
What does insulin do overall to liver, muscle, fat?
Insulin stimulates utilization and storage of glucose, amino acids, and fatty acids, while inhibits breakdown of glycogen, protein, and fat.
What does insulin do to glucose transportation & metabolism?
increases translocation of GLUT transporters to cell membrane
increases glucokinase
stimulates glycogen synthase
inhibits glycogen phosphorylase
What are the 2 types of Type I diabetes?
Type 1A: autoimmune
Type 1B: nonautoimmune, idiopathic
What do beta blockers do to patients with diabetes?
can cause hypoglycemia by depleting catecholamines & their gluconeogenesis & glycogenolysis
What’s the deal with salicylates?
lower blood glucose by increasing pancreatic sensitivity to glucose–promote insulin secretion in Type 2 diabetics & non-diabetics.
What is the pathogenesis of Type 2 DM?
hyperglycemia sometimes insulin secretory dysfunction increased insulin resistance (muscle, fat, liver) increased endogenous glucose production deranged adipocyte bio decreased incretin effect
what are the symptoms of diabetes?
Polyuria (urinating frequently) Polydipsia (very thirsty) Continuous hunger Weight loss Other symptoms Fatigue Dry skin Frequent infections
Complications: Retinopathy Feet ulceration Nephropathy Cardiomyopathy Neuropathy Loss of sensibility in inferior extremities (legs)
What are some important lifestyle changes for diabetes?
increased physical activity (30 min walk/day)
good diet, lower in fat & carbs
weight loss
taking: insulin, oral hypoglycemics
Diabetes management should be individualized for patients with a1c<____.
7%
Preprandial glucose & postprandial glucose should be what for patients with diabetes?
preprandial: 70-130
postprandial: <180
What should LDL & TG be maintained at for diabetic patients?
LDL<150
