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muscle; Regulates glucagons; synthesized & released in response to change in blood fuel levels
GLUCAGON Counterregulates insulin; Maintains fuel availability in absence of dietary glucose; Acts on liver and adipocytes; Synthesized & released in response to change in blood fuel levels Receptor coupled to AC and cAMP production
Signal Transduction Mech. Bl. Glu. Levels required for release Type of receptor Intracellular 2nd Msgr MOA
Binds to pl mem receptor on target cell Receptor cytosolic side has tyrosine kinase activity
High
Low
Tyrosine Kinase Insulin receptor substrate (IRS-1) Reverses glucagons-stimulated phosphorylation Uses phosphorylation cascade to phosphorylate several enzymes o Induces & represses synthesis of certain enzymes o Acts as growth factor to stimulate protein synthesis o Stimulates glucose & aa uptake into cells Receptor internalization, Low glucose levels cause rapid removal from circulation and degradation in liver Anabolic, uptake glucose, store nutrients o o Polypeptide, two strands held together by 2 disulfide bonds Coprecipitates w/ Zinc ions, due to insolubility cell of pancreas Preprohormone on ribosome of rER Prohormone in rER, forms disulfide bonds Packaged in Golgi C-peptide cleaved out in storage vesicles containing zinc ions High glucose levels through GLUT-2high ATP levelsinhibits K+pump to allow ions out of celldepolarization of membrane due to Ca2+ influxfusion of exocytotic vesicles w/pl mem to release insulin to blood stream (passes peripheral
x x
x x
Activated ProtKinaseA phosphorylates Ser residues of reg. enz. in fat & carb metab. Acts on CREBs to initiate enz transcription
Termination of Gs protein activation (GTP hydrolysis) o Phosphodiesterase degradation of cAMP Rapid signal termination Mobilization and utilization of nutrients Polypeptide, 29 aa, MW 3,500 Plasma T1/2 is 3-5min. cell of pancreas Preprohormone on ribosome of rER Prohormone in rER lumen Proteolytic cleavage to 29aa mature glucagon Regulated by [glucose] & [insulin] Secretes into pancreatic ducts bloodsteam
Site/Mode of Secretion
Release Signals
cells to suppress glucagon secretion High bl. glucose AA Vagus nerve (ANS) GIP (gastric inhibitory prot)
Catecholamines Cortisol
Gut hormones AA