Prolonged elevation of plasma free fatty acids desensitizes the insulin secretory response to glucose in vivo in rats.

作者：Timothy M. Mason, Tracy T. Goh, Vaja Tchipashvili, Harmanjit Sandhu, Neehar Gupta, Gary F. Lewis, Adria Giacca · 发表于：Diabetes · 年份：1999 · DOI：10.2337/diabetes.48.3.524 · 被引用次数：181 · 研究领域：Pancreatic function and diabetes、Diabetes and associated disorders、Diet, Metabolism, and Disease

Prolonged exposure of pancreatic islets to free fatty acids (FFAs) inhibits glucose-stimulated insulin secretion (GSIS) in vitro. However, FFA inhibition of GSIS has not been clearly demonstrated in vivo. We examined the in vivo effect of prolonged elevation of plasma FFAs on GSIS using a two-step hyperglycemic clamp in rats treated with a 48-h intravenous infusion of either 20% Intralipid plus heparin (INT) (5 microl/min plus heparin, 0.1 U/min; n = 8), oleate (OLE) (1.3 microEq/min; n = 6), saline (SAL) (n = 6), or bovine serum albumin (BSA) (vehicle for OLE; n = 5). Because there was no difference in any of the parameters between BSA and SAL rats, these groups were combined as control rats (CONT) (n = 11). At the end of the 48-h OLE/INT/CONT infusions, after an overnight fast, plasma glucose was clamped for 2 h at 13 mmol/l and for another 2 h at 22 mmol/l. Preclamp plasma FFAs were elevated twofold (P < 0.01) versus CONT with both INT and OLE (NS, INT vs. OLE). Preclamp glucose, insulin, and C-peptide levels were higher in INT than in CONT rats (P < 0.05), suggesting insulin resistance, but they were not different in OLE and CONT rats. The insulin and C-peptide responses to the rise in plasma glucose from basal to 13 mmol/l were lower in OLE (336 +/- 72 pmol/l and 1.2 +/- 0.1 nmol/l, P < 0.01 and P < 0.05, respectively) than in CONT (552 +/- 54 and 1.9 +/- 0.1) rats, but they were not different between CONT and INT rats (648 +/- 150 and 2.0 +/- 0.4). The insulin and C-pep...