Induction of acute hyperglycemia, hyperlactemia and hypocalcemia in fed and fasted BALB/c mice by intravenous amylin injection.
Amylin has been reported to influence carbohydrate metabolism in rats, dogs and cats. We report here that intravenous injection of 50 micrograms amylin (640 nmol/kg) induced hyperglycemia, hyperlactemia, and hypocalcemia in both fed and 5-hour fasted mice. Peak glucose and lactate increments occurred within 15 minutes of treatment, followed by a slower decline of plasma calcium levels. To determine dose-response characteristics of these effects, fasted animals were given amylin doses ranging from 0.005 micrograms to 500 micrograms (64 pmol/kg to 6.4 mumol/kg). Median effective doses (ED50) for the hyperglycemic, hyperlactemic, and hypocalcemic effects were 155, 16.9 and 190 nmol/kg, respectively, with maximum increases of 6.27 mM for glucose, 1.85 mM for lactate and maximum decrease of 0.37 mM for calcium. The estimated half-life (t1/2) of exogenous amylin in the circulation was 5.0 minutes in fasted mice. These results indicate that amylin is bioactive in mice. The kinetic data predict that biologically effective doses of exogenous amylin result in plasma concentrations comparable to pathophysiological concentrations of endogenous hormone previously reported.
Wang
M W
MW
Department of Physiology, Amylin Pharmaceuticals, Inc., San Diego, California 92121.
Carlo
P
P
Fineman
M
M
Rink
T J
TJ
Young
A A
AA
D000682:Amyloid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005260:Female; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C
D000682:Amyloid; D001786:Blood Glucose; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D019344:Lactic Acid; D002118:Calcium