Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon.
Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon.
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DOI：
10.1007/s00125-008-1082-0
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发表时间：
2008-09
期刊：
影响因子：
8.2
通讯作者：
Rorsman, P.
中科院分区：
文献类型：
--
作者：
Collins, S. C.;Salehi, A.;Eliasson, L.;Olofsson, C. S.;Rorsman, P.
长期暴露于NEFAs会抑制葡萄糖诱导的胰岛素分泌。我们测试了另外两种主要的胰岛激素——生长抑素和胰高血糖素的释放是否也受到影响。小鼠胰岛在4.5或15 mmol/l葡萄糖和或不含0.5 mmol/l油酸或棕榈酸盐的条件下培养72小时。测定胰高血糖素和生长抑素在1或20 mmol/l葡萄糖条件下培养1 h后的释放情况以及两种激素在胰岛中的含量。用电镜观察脂质诱导的胰岛细胞超微结构变化。与4.5 mmol/l葡萄糖培养相比，15mmol /l葡萄糖培养使胰岛胰高血糖素含量增加了约50%。油酸盐或棕榈酸盐使胰岛胰高血糖素含量降低25%（在4.5 mmol/l葡萄糖条件下）至50%（在15 mmol/l葡萄糖条件下）。长期暴露于NEFA下，1 mmol/l葡萄糖水平下胰岛胰高血糖素分泌增加50% （15 mmol/l葡萄糖培养时）至100%（培养基中葡萄糖为4.5 mmol/l）， 20 mmol/l葡萄糖对胰高血糖素分泌的抑制作用消失。生长抑素含量不受葡萄糖和脂类的影响，但无论培养基中是否含有4.5或15 mmol/l的葡萄糖，长期暴露于NEFA中的任何一种后，葡萄糖诱导的生长抑素分泌减少了~ 50%。在非β细胞中<10%可见脂质沉积的超微结构证据，而在β细胞中占80%。长期暴露于高葡萄糖和/或NEFA影响生长抑素和胰高血糖素的释放。对胰高血糖素分泌的影响非常明显，2型糖尿病患者体内由于缺乏胰岛素可能加重高血糖作用。
Long-term exposure to NEFAs leads to inhibition of glucose-induced insulin secretion. We tested whether the release of somatostatin and glucagon, the two other major islet hormones, is also affected. Mouse pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet content of the two hormones were determined. Lipid-induced changes in islet cell ultrastructure were assessed by electron microscopy. Culture at 15 mmol/l glucose increased islet glucagon content by ∼50% relative to that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50% (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin content was unaffected by glucose and lipids, but glucose-induced somatostatin secretion was reduced by ∼50% following long-term exposure to either of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l glucose. Ultrastructural evidence of lipid deposition was seen in <10% of non-beta cells but in >80% of the beta cells. Long-term exposure to high glucose and/or NEFA affects the release of somatostatin and glucagon. The effects on glucagon secretion are very pronounced and in type 2 diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.
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