The present report aims mainly at a reevaluation of salivary glucose concentration and excretion in unstimulated and mechanically stimulated saliva in both normal and diabetic subjects. In normal subjects, a decrease in saliva glucose concentration, an increase in salivary flow, but an unchanged glucose excretion rate were recorded when comparing stimulated saliva to unstimulated saliva. In diabetic patients, an increase in salivary flow with unchanged salivary glucose concentration and glucose excretion rate were observed under the same experimental conditions. Salivary glucose concentration and excretion were much higher in diabetic patients than in control subjects, whether in unstimulated or stimulated saliva. No significant correlation between glycemia and either glucose concentration or glucose excretion rate was found in the diabetic patients, whether in unstimulated or stimulated saliva. In the latter patients, as compared to control subjects, the relative magnitude of the increase in saliva glucose concentration was comparable, however, to that of blood glucose concentration. The relationship between these two variables was also documented in normal subjects and diabetic patients undergoing an oral glucose tolerance test.

In order to gain information on the determinism of the perturbation of fuel homeostasis in situations characterized by a depletion in long-chain polyunsaturated omega3 fatty acids (omega3), the metabolic and hormonal status of omega3-depleted rats (second generation) was examined. When required, these rats were injected intravenously 120 min before sacrifice with a novel medium-chain triglyceride-fish oil emulsion able to provoke a rapid and sustained increase of the omega3 content in cell phospholipids. The measurement of plasma glucose, insulin, phospholipid, triglyceride, and unesterified fatty acid concentration indicated modest insulin resistance in the omega3-depleted rats. The plasma triglyceride and phospholipid concentrations were decreased in the omega3-depleted rats with abnormally low contribution of omega3 in both circulating and pancreatic islet lipids. The protein, insulin, and lipid content of the islets, as well as their intracellular and extracellular spaces, were little affected in the omega3-depleted rats. The metabolism of D-glucose in the islets of omega3-depleted rats was characterized by a lesser increase in D-[5-3H]glucose utilization and D-[U-14C]glucose oxidation in response to a given rise in hexose concentration and an abnormally low ratio between D-glucose oxidation and utilization. These abnormalities could be linked to an increased metabolism of endogenous fatty acids with resulting alteration of glucokinase kinetics. The release of insulin evoked by D-glucose, at a close-to-physiological concentration (8.3 mM), was increased in the omega3-depleted rats, this being considered as consistent with their insulin resistance. Relative to such a release, that evoked by a further rise in D-glucose concentration or by non-glucidic nutrients was abnormally high in omega3-depleted rats, and restored to a normal level after of the intravenous injection of the omega3-rich medium-chain triglyceride-fish oil emulsion. Because the latter procedure failed to correct the perturbation of D-glucose metabolism in the islets of omega3-depleted rats, it is proposed that the anomalies in the secretory behaviour of islets in terms of their response to an increase in hexose concentration or non-nutrient secretagogues is mainly attributable to alteration in K+ and Ca2+ handling, as indeed recently documented in separate experiments.

Presently an insufficient supply of long-chain polyunsaturated omega3 fatty acid is prevalent in Western populations leading to potential metabolic consequences. Based on this fact, this study deals mainly with various aspects of lipid metabolism in second generation female omega3-depleted rats. The parametrial fat and body weights were higher in omega3-depleted than control animals. This coincided with liver steatosis but did not alter heart triglyceride/phospholipid ratio. The net uptake of [U-14C] palmitate by adipocytes was also higher in omega3-depleted rats than in control animals. The uptake of D-[U- 4C] glucose or [1,2 (-14)C] acetate by adipocytes was lower, however in omega3-depleted than control animals and was unaffected by insulin in the former as distinct from latter animals. Despite comparable basal lipolysis, the increase in glycerol output from adipocytes provoked by theophylline was higher in omega3-depleted than control rats. The fatty acid pattern of lipids in adipose tissue was characterized in the omega3-depleted rats by a much lower omega3 content, higher apparent Delta 9-saturase and elongase activities, lower efficiency for the conversion of C18:2omega6 to C20:4omega6 and higher efficiency for the conversion of C18:3omega3 to C20:5omega3. These features were compared to those prevailing in liver and plasma lipids. The present study thus extends knowledge on the alteration of lipid metabolism resulting from a deficiency in long-chain polyunsaturated omega3 fatty acids.

Abstract. Second generation rats depleted in long-chain polyunsaturated ˆ3 fatty acids are currently used as an animal model for the insufficient dietary supply of such fatty acids often prevailing in Western populations. The present study deals mainly with the effects of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO), as compared to a control medium-chain triglyceride:olive oil emulsion (MCT: OO), administered as an intravenous bolus to the ˆ3-depleted rats 60-120 min before sacrifice upon selected biochemical and biophysical variables. The major findings consisted of a severe decrease of the ˆ3 fatty acid content of liver lipids in non-injected ˆ3-depleted rats and its partial correction after injection of the MCT:FO emulsion. The ˆ3-depleted rats also displayed liver steatosis, increased incorporation of long-chain polyunsaturated ˆ6 fatty acids in liver phospholipids and increased activity of liver Δ9-desaturase. As judged from the effects of ouabain upon 86 Rb net uptake by isolated pancreatic islets, the activity of Na + ,K + -ATPase was virtually abolished in the ˆ3-depleted rats. The latter defect was corrected by prior intravenous injection of the MCT:FO emulsion, this coinciding with suppression of the excessive secretory response to a number of insulin secretagogues otherwise observed in the islets of ˆ3-depleted rats injected or not with the MCT:OO emulsion.

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...