The Effect Of Elevated Free Fatty Acid Levels On The Pancreatic Beta-cell Function In Vivo

Objective: Circulating free fatty acids (FFA) are elevated in subjects with metabolic syndrome and type 2 diabetes. Studies in vitro showed that prolonged exposure to FFA had caused reduced glucose stimulated insulin secretion (GSIS) and apoptosis of human pancreatic beta-cells, but the results conducted in vivo were rare and not consistent. In an effort to better understand the phenomenon of lipotoxicity in beta-cells, we evaluated the effects of infusion of a triglyceride emulsion in Sprague-Dawley (S-D) rats on basal and GSIS in pancreatic beta-cell in vivo and investigated the possible mechanisms.Materials and Methods: The studies were composed of two parts. Part one: male S-D rats underwent 2-6 days infusions in two groups. Control group (NS, n=10): normal saline alone; FFA group (FFA, n=15): 20% intralipid + heparin (intralipid: heparin = 1ml: 40IU), infusion rates varied from 0.6 -1.8 ml/h to maintain circulating FFA concentration at 2 - 3 times above the baseline. The pancreatic tissues were harvested at the end of infusion and the isolated pancreas were perfused with Kerbs-Ringer bicarbonated (KRB) buffer contained with 3.0 mmol/L and 16.7 mmol/L glucose respectively. And the expression of insulin (INS) in pancreatic islets was examined by immunohistochemistry. Part two: male S-D rats underwent 4 days infusions in three groups. Controls group (NS, n=5): normal saline alone; FFA group (FFA, n=5): 20% intralipid + heparin, infusion rates varied from 0.6 -1.2...