Reversibility of metabolic and morphological changes associated with chronic exposure of pancreatic islet beta-cells to fatty acids.
Pancreatic beta-cells metabolise both lipid and glucose nutrients but chronic exposure (>24 h) to elevated fatty acid (FA) concentrations results in deleterious metabolic and morphological changes. The aims of this study were to assess the adaptive morphological, metabolic and secretory responses of islet beta-cells to exposure and removal of FA. Isolated mouse islets and INS-1 beta-cells were exposed to oleate or palmitate (0.5 mM) or a 1:1 mixture of both FA for 48 h prior to a 24 h period without FA. Subsequent changes in lipid storage and composition (triglycerides, TG and phospholipids, PL), gene expression, beta-cell morphology and glucose-stimulated insulin secretion (GSIS) were determined. Intracellular TG content increased during exposure to FA and was lower in cells subsequently incubated in FA-free media (P < 0.05); TG storage was visible as oil red O positive droplets (oleate) by light microscopy or 'splits' (palmitate) by electron microscopy. Significant desaturation of beta-cell FA occurred after exposure to oleate and palmitate. After incubation in FA-free media, there was differential handling of specific FA in TG, resulting in a profile that tended to revert to that of control cells. FA treatment resulted in elevated lipolysis of intracellular TG, increased FA oxidation and reduced GSIS. After incubation in FA-free media, oxidation remained elevated but inhibition of FA oxidation with etomoxir (10 microM) had no effect on the improvement in GSIS. The beta-cell demonstrates metabolic flexibility as an adaptive response to ambient concentrations of FA.
Pinnick
Katherine
K
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.
Neville
Matt
M
Clark
Anne
A
Fielding
Barbara
B
D000222:Adaptation, Physiological; D000818:Animals; D048430:Cell Shape; D002478:Cells, Cultured; D005227:Fatty Acids / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology; D010168:Palmitates / Q000494:pharmacology
D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D010168:Palmitates; D019301:Oleic Acid