INSULIN Role in metabolic Homeo-stasis Major anabolic hormone; Promotes storage of nutrients, glucose uptake in liver, adipocytes, skeletal

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

EPINEPHRINE Insulin counterregulato ry hormone

CORTISOL Insulin counterregulator y hormone

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

Catecholamine: act as either NTS, or Hormone Low

High

Low

Binds intracellular receptors acts on nuclear chromatin 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

AC coupled receptor cAMP o

x x

x x

Activated ProtKinaseA phosphorylates Ser residues of reg. enz. in fat & carb metab. Acts on CREBs to initiate enz transcription

Signal Termi-nation Genl Effects Structure Site/Mode of Synthesis

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