Fatty acid inhibition of glucose-stimulated insulin secretion is enhanced in pancreatic islets from insulin-resistant rats.
A study was initiated to test two hypotheses. The first was the postulate that glucose-stimulated insulin secretion would be enhanced in pancreatic islets isolated from normal non-obese rats made insulin-resistant by dietary means. The second, related hypothesis was that glucose-stimulated insulin secretion by pancreatic islets isolated from insulin-resistant rats would be more vulnerable to inhibition following culture in the presence of fatty acids. For this purpose, insulin resistance was induced in normal Sprague-Dawley rats by feeding fat-enriched and fructose-enriched diets. The results indicate that islets isolated from either fat-fed or fructose-fed rats secreted significantly more insulin at a glucose concentration of 2.5 to 10.0 mmol/L. In addition, the mean maximal glucose (27 mmol/L)-stimulated insulin secretion rate was significantly lower (15.3 +/- 2.5 ng/islet/h) in islets from fructose-fed rats versus chow-fed rats (25.2 +/- 3.1 ng/islet/h) following culture for 48 hours in the presence of palmitate (0.125 micromol/L). These results support the view that glucose-stimulated insulin secretion is enhanced in islets from insulin-resistant rats, and that these islets are more vulnerable to the inhibitory effects of free fatty acid (FFA) on insulin secretion.
Chen
N G
NG
Department of Medicine, Stanford University School of Medicine, CA, USA.
Reaven
G M
GM
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004041:Dietary Fats; D007328:Insulin; D019308:Palmitic Acid; D005632:Fructose; D005947:Glucose