Insulin-like growth factor-I inhibits insulin and amylin secretion in conscious rats.
Human recombinant insulin-like growth factor-I (IGF-I) exerts insulin-like antidiabetic properties in vitro and in vivo. To determine the effects of IGF-I infusion on insulin and amylin release, plasma glucose of freely moving undisturbed rats was constantly maintained at 13.9 mmol/liter by variable glucose infusion for 120 min in three groups of fasted Sprague-Dawley rats (hyperglycemic clamp technique). Group A, vehicle infusion (control group); group B, bolus 0.39 nmol plus 0.39 nmol/h IGF-I continously; and group C, bolus 1.96 nmol plus 1.96 nmol/h IGF-I continuously. During the steady-state phase of the experiment, IGF-I dose dependently reduced plasma insulin (pmol/liter: A, 718 +/- 58; B, 613 +/- 35, NS vs. A; C, 408 +/- 21, P < 0.01 vs. A; dose-response effect: P < 0.0001), plasma amylin (pmol/liter: A, 10.2 +/- 0.6; B, 8.8 +/- 0.5, NS vs. A; C, 5.8 +/- 0.4, P < 0.01 vs. A; dose-response effect: P < 0.0001), and net glucose uptake (mumol/kg.min: A, 188 +/- 12; B, 160 +/- 12, NS vs. A; C, 134 +/- 7, P < 0.01 vs. A; dose-response effect: P < 0.0025). At the same time, the ratio of plasma insulin/plasma amylin (mol/mol: A, 72 +/- 6; B, 71 +/- 5; C, 74 +/- 9; NS), the ratio of net glucose uptake/plasma insulin (mumol/kg.min per pmol/liter: A, 0.28 +/- 0.03; B, 0.27 +/- 0.02; C, 0.36 +/- 0.04; NS), and glycogen content of liver, heart, and various hindlimb muscles remained unaffected. The results demonstrate that IGF-I is a potent inhibitor of insulin and amylin release in healthy rats exposed to hyperglycemia and suggest that IGF-I infusion inhibits hormone secretion from pancreatic beta cells at infusion rates that do not affect insulin-stimulated glucose uptake by peripheral tissues.
Division of Endocrinology and Metabolism, University of Vienna, Austria.
C
C
Fürnsinn
M
M
Alma
M
M
Roden
T
T
Pieber
P
P
Nowotny
B
B
Schneider
W
W
Waldhäusl
D000682:Amyloid / Q000097:blood*; D000818:Animals; D003243:Consciousness / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D006706:Homeostasis; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D058228:Islet Amyloid Polypeptide; D008099:Liver / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D005947:Glucose