Fat-induced changes in mouse pancreatic islet insulin secretion, insulin biosynthesis and glucose metabolism

Abstract

Insulin secretion, insulin biosynthesis and islet glucose oxidation were studied in pancreatic islets isolated from fat-fed diabetic mice of both sexes. Insulin secretion from isolated islets was studied after consecutive stimulation with alpha-ketoisocaproic acid + glutamine, glucose, forskolin, and 12-O-tetradecanoylphorbol 13-acetate. Glucose-induced insulin secretion was impaired in islets from fat-fed mice. This was associated with a reduction of approximately 50% in islet glucose oxidation. Islet insulin secretion stimulated by the non-carbohydrate secretagogues tended to be higher in the fat-fed mice, but a statistically significant effect was not observed. Pancreatic insulin content was reduced by 50%, whereas the islet insulin and DNA content was unchanged after fat feeding. Proinsulin mRNA was reduced by 35% in islets from fat-fed mice, and was associated with a reduction of approximately 50% in glucose-stimulated (pro)insulin biosynthesis. It is concluded that the insulin secretory response of islets isolated from fat-fed mice is similar to the secretory pattern known from human type 2, non-insulin-dependent diabetics, and that a defect in islet glucose recognition, resulting in decreased glucose oxidation, may be responsible for the observed insulin secretory and biosynthetic defects seen after glucose stimulation.

Pleiotropic effects of fatty acids on pancreatic β‐cells

“…Investigation with isolated islets from 3-h lipid-infused rats show that the response to 27 mM glucose is enhanced, but after 48 h of intralipid infusion, the glucose-induced insulin release is reduced (Sako and Grill, 1990). Qualitatively, similar results have been observed in insulin secretory responses of humans with type 2 diabetes (Capito et al, 1992). Several studies (Prentki et al, 1992;Chen et al, 1994;Opara et al, 1994;Stein et al, 1997) have shown the importance of the type of FA on the process of glucose-induced insulin secretion in fed rats.…”

Beta-cell hypersensitivity to glucose following 24-h exposure of rat islets to fatty acids

“…Possible mechanisms based on known modulatory effects of fatty acids include acylation [29], increased gene transcription [30], increased production of long chain-CoA products, or a direct effect of fatty acid metabolites on the enzyme activity. Regarding the latter, an inhibitory effect of long chain acyl-CoA esters has been reported for glucokinase [31,32], phosphofructokinase [33], and glucose 6-phosphatase [34]: we are not aware of any reports of stimulation of a glycolytic enzyme such as that noted in this study. No attempt to address these different possibilities was made in this study.…”

Soybean oil treatment impairs glucose-stimulated insulin secretion and changes fatty acid composition of normal and diabetic islets

“…The similarity between fatty acids' effects on the insulin secretory response of isolated islets and the mechanisms underlying type 2 diabetes has been described [3,4]. The influence of free fatty acid (FFA) on insulin secretion is associated with the suppression of peripheral glucose uptake, stimulation of hepatic gluconeogenesis, defect in islet glucose recognition and fatty acid oxidation, as stated in the fuel concept and the Randle cycle hypothesis, the latter also known as the glucose-fatty acid cycle [5][6][7][8][9][10].…”