Pancreatic islet function in ω-3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release

Abstract

islet function in -3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release. Am J Physiol Endocrinol Metab 291: E441-E448, 2006; doi:10.1152/ajpendo.00455.2005.-Considering the insufficient supply of long-chain polyunsaturated -3 fatty acids often prevailing in Western populations, this report deals mainly with alterations of Ca 2ϩ fluxes and Ca 2ϩ -dependent insulin secretory events in isolated pancreatic islets from -3-depleted rats. In terms of 45 Ca 2ϩ handling, the islets from -3-depleted rats, compared with those from normal animals, displayed an unaltered responsiveness to an increase in extracellular K ϩ concentration, a lower inflow rate and lower fractional outflow rate of the divalent cation, and higher 45 Ca 2ϩ -labeled cellular pool(s) at isotopic equilibrium. The latter anomaly was corrected 120 min after intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a control -3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM D-glucose, insulin release was higher in islets from -3-depleted rats vs. control animals, coinciding with a higher cytosolic Ca 2ϩ concentration. The relative magnitude of the increase in insulin output attributable to a rise in D-glucose as well as extracellular Ca 2ϩ or K ϩ concentration, to the absence vs. presence of verapamil and to the presence vs. absence of extracellular Ca 2ϩ , theophylline, phorbol 12-myristate 13-acetate, or Ba 2ϩ , was always more pronounced in islets from -3-depleted rats injected with the MCT:OO compared with the MCT:FO emulsion. A comparable situation prevailed when comparing islets from noninjected -3-depleted and normal rats. In light of these and previous findings, we propose that an impairment of Na ϩ ,K ϩ -ATPase activity plays a major, although not an exclusive, role in the perturbation of Ca 2ϩ fluxes and Ca 2ϩ -dependent secretory events in the islets from -3-depleted rats.long-chain polyunsaturated -3 fatty acid-depleted rats; calcium fluxes; pancreatic islets BECAUSE OF THE PRESENTLY FREQUENT occurrence of a depletion in long-chain polyunsaturated -3 fatty acids in Western populations and its consequences in terms of the control of fuel homeostasis (1, 3, 12, 13), we have recently characterized several metabolic and hormonal variables in -3-depleted rats (second generation) and investigated their possible correction within 60 -120 min after the bolus intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion found to provoke a rapid enrichment of cell phospholipids in C20:5-3 and C22:6-3 in both normal human subjects and either normal or -3-depleted rats (10, 11). Selected metabolic, cationic, and secretory variables also were examined in isolated pancreatic islets (2, 6, 8) prepared from the -3-depleted rats and compared with those measured in islets from either normal rats or -3-depleted animals injected intravenously 120 min before death with the MCT:FO emulsion or a control -3 fatty acid-poor medium-chain triglyceride-olive oi...

Rapid changes in liver lipid composition and pancreatic islet K+ handling and secretory behaviour provoked by the intravenous administration of a medium-chain triglyceride:fish oil emulsion to long-chain polyunsaturated ω3 fatty acid-depleted rats

“…Last, the secretory data collected in the present study (Table VI) again extend prior observations (5,8) indicating that, relative to the release of insulin recorded in the sole presence of 8.3 mM D-glucose, that found in the concomitant presence of other insulin secretagogues is significantly lower in the islets from ˆ3-FO rats than in those from ˆ3-OO rats. A comparable situation is found when comparing islets from control rats to those obtained from ˆ3-NI rats (5,8).…”

“…A comparable situation is found when comparing islets from control rats to those obtained from ˆ3-NI rats (5,8).…”

“…items as plasma D-glucose and insulin concentration (5), liver phospholipid and triglyceride fatty acid content and pattern (4), pancreatic islet protein and insulin content (5), and both 86 Rb net uptake (9) and insulin secretion (5,8) by isolated islets. In these respects, emphasis is here placed on the comparison between ˆ3-depleted rats injected 60-120 min before sacrifice with either MCT:FO or MCT:OO.…”

“…Previous investigations have documented that these ˆ3 rats display several features of metabolic syndrome including visceral obesity (3), liver steatosis (4), insulin resistance (5), hypertension (6) and cardiac hypertrophy (7). Perturbation of metabolic, ionic and secretory variables were also observed in the pancreatic islets of ˆ3 rats (5,8,9).…”

The metabolic syndrome of fructose-fed rats: Effects of long-chain polyunsaturated ω3 and ω6 fatty acids. I. Intraperitoneal glucose tolerance test

“…Taken as a whole, these results suggest that, in the (Fsal) rats, a modest improvement of insulin sensitivity was opposed, in terms of glucose homeostasis, by a decreased secretory response of insulin-producing cells to a rise in plasma D-glucose concentration. The latter situation is reminiscent of that recorded in isolated pancreatic islets, when comparing the insulinotropic action of several secretagogues in islets from 2nd generation ω3-depleted rats to that of control animals both exposed to diets not enriched with D-fructose, the output of insulin being higher in the ω3-depleted rats than in the control animals (11,12).…”