优降糖继发失效患者对葡萄糖及胰升糖素的不同反应

Different responses of β cell to glucagon and glucose in type 2 diabetic patients with secondary failure to glibenclamide

目的了解优降糖继发失效的２型糖尿病患者对不同胰岛素刺激物的反应，探讨线粒体基因第３２４３位点Ａ→Ｇ突变在优降糖继发失效病因学的作用。方法对２８例优降糖继发失效患者进行胰升糖素刺激试验及标准馒头餐试验，并筛查线粒体ＤＮＡ第３２４３位点Ａ→Ｇ的突变。结果失效组与有效组比较，空腹及胰升糖素刺激后６分钟血清Ｃ肽水平没有显著差别，但餐后１、２、３小时胰岛素、Ｃ肽值明显降低（Ｐ均＜０．０１），高峰值在餐后２小时（胰岛素１３８６±７０２ｐｍｏｌ／Ｌ对２５２７±１２５３ｐｍｏｌ／Ｌ，Ｃ肽１５９８±４５４ｐｍｏｌ／Ｌ对２７０６±９４３ｐｍｏｌ／Ｌ，Ｐ均＜０．０１）。聚合酶链反应（ＰＣＲ）结合ＡｐａＩ酶切的方法未在２８例继发失效患者中检出外周血线粒体ＤＮＡ第３２４３位点Ａ→Ｇ的突变。结论在优降糖继发失效的２型糖尿病患者，以胰升糖素刺激试验评估的胰岛素分泌功能无明显减退，但胰岛β细胞选择性对葡萄糖刺激胰岛素分泌的反应下降；线粒体基因３２４３位点Ａ→Ｇ突变不是优降糖继发失效的常见原因。

Objective To evaluate the mechanism of secondary failure to glibenclamide in type 2 diabetic patients and the role of mitochondrial gene position 3243 point mutation (A→G) in the etiology of secondary failure. Methods A group of 28 cases of type 2 diabetics with secondary failure to glibenclamide (non responders), and another group of 23 cases of responders were studied for the response to glucagon and glucose, and the nonresponders were tested for the position 3243 point mutation (A→G) in mitochondrial DNA with polymerase chain reaction (PCR) and restriction enzyme Apa I. Results Fasting and 1h, 2h and 3h serum glucose levels after standard steamed bread meal were higher in nonresponders as compared with responders, (P<0.01). Both fasting insulin and C peptide were similar between the two groups (P>0.05). SowastheglucagonstimulatedC peptide (P>0.05). Meanwhile, insulin and C peptide response to the test meal were reduced at any time point in the nonrespondersthanthoseintheresponders (peak values for insulin 1386±702 vs 2527±1253pmol/L,for C peptide 1598±454 vs 2706±943pmol/L, P<0.01). No A→G mutation in position 3243 of mitochondrial DNA from peripheral blood was found in the nonresponders. Conclusions The reduced response of insulin reaction to test meal contributes to secondary failure to glibenclamide in type 2 diabetic patients and position 3243 gene mutation in mitochondrial DNA is not the common cause of secondary failure to glibenclamide.