Long-term exposure of INS-1 rat insulinoma cells to linoleic acid and glucose in vitro affects cell viability and function through mitochondrial-mediated pathways.

摘要: Obesity with excessive levels of circulating free fatty acids (FFAs) is tightly linked to the incidence type 2 diabetes. Insulin resistance peripheral tissues and pancreatic β-cell dysfunction are two major pathological changes in diabetes both facilitated by FFAs and/or glucose. To gain insight into mitochondrial-mediated mechanisms which long-term exposure INS-1 cells excess causes dysfunction, effects unsaturated FFA linoleic acid (C 18:2, n-6) on rat insulinoma β was investigated. were incubated 0, 50, 250 or 500 μM acid/0.5% (w/v) BSA for 48 h under culture conditions normal (11.1 mM) high (25 glucose serum-free RPMI-1640 medium. Cell viability, apoptosis, glucose-stimulated insulin secretion, Bcl-2, Bax gene expression levels, mitochondrial membrane potential cytochrome c release examined. Linoleic significantly suppressed cell viability induced apoptosis when administered 11.1 25 mM Compared control, increased medium but not also dose-dependently reduced (ΔΨm) promoted from mitochondria medium, further reducing dependent function. With increase secretion function deteriorated further. The results this study indicate that chronic acid-induced involved a signal pathway, enhanced dysfunction.