Amylin-mediated reduction in insulin sensitivity corresponds to reduced insulin receptor kinase activity in the rat in vivo.
Studies were undertaken to elucidate further the mechanism whereby the pancreatic peptide amylin induces insulin resistance. Sixteen male Sprague-Dawley rats underwent hyperinsulinemic (14 pmol/kg/min, 0 to 120 minutes) euglycemic clamps in the presence or absence of amylin (500 pmol/kg/min, 60 to 120 minutes). Amylin induced insulin resistance at both the hepatic level (mean +/- SE: hepatic glucose output [HGO] with amylin 1.4 +/- 0.2 v without amylin -1.9 +/- 0.3 mmol/kg/h, P < .001) and peripheral level (glucose disposal [Rd] with amylin 5.0 +/- 0.2 v without amylin 8.5 +/- 0.6 mmol/kg/h, P < .001). Serum insulin levels were similar in the presence or absence of amylin alone (661 +/- 89 v 636 +/- 50 pmol/L, respectively, P = NS), but were significantly less when somatostatin (SRIF) was simultaneously infused (408 +/- 15 pmol/L, P < .02 v the other two groups). This suggests that endogenous insulin production was not suppressed by amylin under these study conditions. Similar findings were obtained in 18 animals in the absence of exogenous insulin infusion. In vitro kinase activity toward histone of skeletal muscle insulin receptors (IRs) activated by insulin in vivo was reduced in the presence of amylin to 6.0 +/- 0.8 versus 9.1 +/- 1.2 fmol phosphate into histone (insulin-infused) and 3.9 +/- 0.7 versus 6.9 +/- 1.4 (non-insulin-infused; P < .03 by ANOVA). Serum calcium was significantly decreased in amylin-treated animals (1.93 +/- 0.04 v 2.30 +/- 0.05 mmol/L, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Bryer-Ash
M
M
Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Follett
L
L
Hodges
N
N
Wimalawansa
S
S
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007329:Insulin Antagonists / Q000494:pharmacology; D007333:Insulin Resistance; D058228:Islet Amyloid Polypeptide; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology
D000682:Amyloid; D007328:Insulin; D007329:Insulin Antagonists; D058228:Islet Amyloid Polypeptide; D013004:Somatostatin; D011972:Receptor, Insulin; D005947:Glucose; D002118:Calcium