Islet amyloid polypeptide amide causes peripheral insulin resistance in vivo in dogs.
Islet amyloid polypeptide is a 37 amino acid hormone-like peptide which is the major protein component of islet amyloid deposits commonly found in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Recent studies indicate that a physiologically active form of this peptide appears to be carboxyamidated and secreted from the insulin-producing beta cell. In order to clarify the possible in vivo actions of islet amyloid polypeptide, we have studied the effects of synthesized islet amyloid polypeptide-amide on peripheral glucose utilization by performing hyperinsulinaemic euglycaemic glucose clamp studies on dogs. Exogenously administered islet amyloid polypeptide-amide (an infusion from 1.0 to 100 micrograms.kg-1.h-1, over 2 h) inhibited the insulin-stimulated glucose disposal rate in a dose dependent manner. Twenty-five micrograms.kg-1.h-1 of islet amyloid polypeptide-amide infused via a peripheral vein significantly lowered the glucose disposal rate by 20% (from 17.4 +/- 1.7 to 14.4 +/- 1.7 mg.kg-1.min-1, n = 5, p less than 0.01). These findings suggest that islet amyloid polypeptide-amide causes peripheral insulin resistance in vivo.
First Department of Medicine, Wakayama University of Medical Science, Japan.
R
R
Sowa
T
T
Sanke
J
J
Hirayama
H
H
Tabata
H
H
Furuta
S
S
Nishimura
K
K
Nanjo
D000682:Amyloid / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004285:Dogs; D015309:Glucose Clamp Technique; D007333:Insulin Resistance; D058228:Islet Amyloid Polypeptide; D007700:Kinetics
D000682:Amyloid; D001786:Blood Glucose; D058228:Islet Amyloid Polypeptide