CHRONIC PERIFUSION OF RAT ISLETS WITH PALMITATE SUPPRESSES GLUCOSE-STIMULATED INSULIN RELEASE
CHRONIC PERIFUSION OF RAT ISLETS WITH PALMITATE SUPPRESSES GLUCOSE-STIMULATED INSULIN RELEASE
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DOI：
10.1210/en.133.1.208
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发表时间：
1993-07-01
期刊：
影响因子：
4.8
通讯作者：
ELKS, ML
中科院分区：
文献类型：
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作者：
ELKS, ML
为了检验肥胖型糖尿病患者的高循环FFA水平可能导致在该条件下观察到的胰岛素分泌动力学改变的假设，在分离的灌流大鼠胰岛细胞中测量了胰岛素释放，不添加或添加棕榈酸酯。与其他系统一样，棕榈酸盐（1 mM）可以刺激胰岛素释放。棕榈酸盐（1 mM）在灌流2、3或4 h后抑制第一和第二相胰岛素释放，但在1 h后不抑制。0.3 mM棕榈酸盐没有显著影响，在1 mM时效果最大。精氨酸的刺激作用基本上不受影响。甲苯磺丁脲（1 mM）逆转或抵消的效果。葡萄糖氧化在与ImM棕榈酸盐孵育4小时的胰岛中被抑制。脂肪氧化抑制剂，α-溴硬脂酸酯（1 mM）和甲基-3-十四烷基缩水甘油酸酯（100 μ M）逆转棕榈酸对葡萄糖刺激的胰岛素释放和葡萄糖氧化的影响。这种抑制可以通过脂肪氧化抑制剂逆转。这支持了以下假设：FFA水平升高和/或脂肪氧化增加可能通过燃料拮抗作用以及先前记录的外周葡萄糖摄取抑制和肝再生刺激导致肥胖糖尿病患者胰岛素分泌动力学改变，并且可能是肥胖和糖尿病发展之间的关键联系。
To test the hypothesis that the high circulating FFA levels in the diabetes of obesity could contribute to the altered dynamics of insulin secretion seen in that condition, insulin release was measured in isolated perifused rat islet cells, without or with added palmitate. Acutely, as in other systems, palmitate (1 mM) stimulated insulin release. Palmitate (1 mM) suppressed both first and second phase insulin release after 2, 3, or 4 h of perifusion, but not after 1 h. No significant effect was noted with 0.3 mM palmitate, and the effect was maximal at 1 mM. The stimulatory effects of arginine were essentially unaffected. Tolbutamide (1 mM) reversed or counteracted the effect. Glucose oxidation was suppressed in islets incubated with 1 mM palmitate for 4 h. Inhibitors of fat oxidation, alpha-bromostearate (1 mM) and methyl-3-tetradecylglycidate (100 muM) reversed the effects of palmitate on glucose-stimulated insulin release and glucose oxidation.Thus, prolonged incubation of rat islet cells with 1 mM palmitate could suppress the glucose-stimulated release of insulin from perifused rat islets. This suppression could be reversed by inhibitors of fat oxidation. This supports the hypothesis that elevated FFA levels and/or increased fat oxidation could contribute to the altered dynamics of insulin secretion in obese diabetics by fuel antagonism as well as the previously documented suppression of peripheral glucose uptake and stimulation of hepatic gluconeogenesis and may be a key link between obesity and the development of diabetes.