高脂肪食投与ラットにおける膵B細胞機能に及ぼす電撃ストレスの影響 (II):単離膵ラ氏島におけるGlucose刺激によるInsulin分泌と細胞内Glucose代謝

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The synergistic effects of dietary obesity produced by the feeding of a high fat diet and stress induced by electric shocks on the rates of insulin secretion, glucose utilization and oxidation in response to glucose, and the contribution of the pentose cycle pathway to glucose metabolism were examined in isolated pancreatic islets from rats fasted overnight. Rats weighing 110 g were fed ad libitum for 12 weeks either a control (50% Starch; C) or a high fat diet (40% Butter; F). Half of the rats on each diet received electric shocks at random, 1 hour per day for the last 3 weeks of the experimental period (group C-S and F-S). The remaining rats were housed in home cages throughout the experiment (group C-NS and F-NS). 1. The rates of insulin secretion in islets from the C-NS group were increased threefold when the glucose concentration was raised from 2 to 25 mM, and the pattern of secretory response to glucose showed a sigmoid curve. The dose-response relation for glucose-stimulated insulin secretion in the C-S group was similar to that in the C-NS group. The rate of insulin secretion to glucose in islets from the F-NS group increased much more than that in the C-NS group with changes in glucose concentration between 5 to 10 mM, but the Vmax value of the secretory response was unchanged. In the F-S group, insulin secretion in islets was markedly diminished with each glucose concentration over 10 mM up to 25 mM. 2. The curves relating to the rates of glucose utilization (as judged by the formation of 3H20 from [5-3H] glucose) to glucose concentration were similar in shape to those showing insulin secretory response to glucose in the C-NS group or in the F-NS group, respectively. The rates of glucose utilization in islets from the F-S group were increased at high glucose concentration (16.7 mM) but extremely lowered at the physiological glucose concentration (from 5 to 10 mM). 3. The rate of [U-14C] glucose oxidation at 16.7 mM glucose in islets from the C groups was unchanged by stress. The rate of glucose oxidation in islets from the F-S group was decreased by 67% of that in the F-NS group or by 55% of that in the C-S group. 4. The absolute rate of glucose metabolized via the pentose cycle pathway at 2 mM glucose in islets from the F-NS group was diminished by 60% of that in the C-NS group. A marked decrease in the absolute rate of glucose metabolism via the pentose cycle pathway was observed in islets from the F-S group. It is concluded that the decreased insulin secretory response to glucose in islets from the high fat fed rats stressed by electric shocks is associated with changes in glucose metabolism, and suggests that the decreased glucose metabolism may be involved in an inability of glucose to stimulate insulin secretion.
日本内分泌学会の論文

高脂肪食投与ラットにおける膵B細胞機能に及ぼす電撃ストレスの影響 (II):単離膵ラ氏島におけるGlucose刺激によるInsulin分泌と細胞内Glucose代謝

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