Insulin Pathophysi Flashcards
insulin receptor structure
dimer of 2 a-domains and 2 b-domains that are disulfide cross-linked
role of A subunits on insulin receptor
regulatory unit of the receptor represses the catalytic activity of beta subunit repression is relieved by insulin binding
role of B subunits on insulin receptor
contain the tyrosine kinase catalytic domains for autophosphorylation so that it can bind insulin receptor substrate (IRS)
effects of insulin on the liver
inhibits glycogenolysis, ketogenesis, and gluconeogenesis
stimulates glycogen synthesis and triglyceride synthesis
effects of insulin on skeletal muscle
stimulates glucose transport and amino acid transport
effects of insulin on adipose tissue
stimulates glucose transport and amino acid transport
PI3K (Phosphatidylinositol 3-kinase)
most prominent protein recruited by IRS in insulin receptor signaling
lipogenesis
glucose stored in adipocytes
glycolysis
utilization of glucose for fuel
glycogen synthesis
storage of glucose
gluconeogenesis
export of glucose
glucose disposal (uptake into tissue) during fasting state
not secreting insulin
75% is insulin non-insulin-dependent: liver, GI, brain
25% is insulin-dependent in skeletal muscle
glucagon is secreted to prevent hypoglycemia
glucose disposal (uptake into tissues during fed state)
80-85% is insulin-dependent in skeletal muscle
4-5% is insulin-dependent in adipose tissue
glucagon secretion is inhibited
insulin inhibits release of FFA from adipose tissue
decreased serum free fatty acids (FFA)
enhances insulin action on skeletal muscle
reduces hepatic glucose production
glucose transporters
GLUT 1
GLUT 2
GLUT 3
GLUT 4
GLUT 1
Km = 1 to 2 mM
constitutive
widely expressed, may be found in B cells
GLUT 2
Km = 15-20 mM (glucose concentration has to be high for glucose transport to occur)
constitutive
found in B-cells
GLUT 3
Km < 1 mM (will transport glucose at very low glucose concentrations)
constitutive
found in neurons
GLUT 4
Km = 5 mM
insulin induced
found in skeletal muscle
B-cells
found in the pancreas
secrete insulin and amylin
endocrine B-cells
secretes into the blood stream
exocrine B-cells
secretes into the small intestine
glucagon
stimulates glycogen breakdown and increase blood glucose secreted by a cells of pancreas
somatostatin
general inhibitor of secretion of a and B cells
secreted by D-cells
insulin
stimulates uptake and utilization of glucose
secreted by B-cells
amylin
co-secreted with insulin
slows gastric emptying
decreases food intake
inhibits glucagon secretion
secreted by B-cells
insulin processing
synthesized as a single peptide and deposited in secretory granules
in secretor granules, insulin is cleaves to A and B chains, and C (connecting) peptides by proconvertase
Zn role in insulin
packs insulin together in tight structures
