RAPID NORMALIZATION STIMULATION BY 1,25-DIHYDROXYVITAMIN-D3 OF INSULIN-SECRETION AND GLUCOSE-TOLERANCE IN THE VITAMIN D-DEFICIENT RAT
RAPID NORMALIZATION STIMULATION BY 1,25-DIHYDROXYVITAMIN-D3 OF INSULIN-SECRETION AND GLUCOSE-TOLERANCE IN THE VITAMIN D-DEFICIENT RAT
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DOI：
10.1210/endo-120-4-1490
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发表时间：
1987-04-01
期刊：
影响因子：
4.8
通讯作者：
NORMAN, AW
中科院分区：
文献类型：
--
作者：
CADE, C;NORMAN, AW
先前在这个实验室中已经证明，维生素D3对于灌注大鼠胰腺的正常胰岛素分泌是必不可少的。最近，我们已经证明，维生素d在这一过程中的生理作用是一致的，维生素d缺乏的大鼠表现出葡萄糖清除和胰岛素分泌受损，通过静脉葡萄糖耐量试验监测。在补充维生素D后，这两个参数都得到了显著改善，而不受营养因素和现行血浆钙磷浓度的影响。本研究研究了单次皮下注射活性代谢物1,25-二羟基维生素D3 [1,25-(OH)2D3]对葡萄糖耐量和胰岛素分泌的剂量反应和时间过程的影响。维生素d缺乏大鼠(KG = 912 +-。1,25 (OH)2D3 （1.3 nmol;20 U）急性给药（KG = 676 .+-）后3小时，KG明显改善。13)，这种清除率可维持20小时（KG = 688 +-）。24)。这种改善与葡萄糖诱导的胰岛素分泌增强相对应。在1,25-(OH)2D3取代后3小时，胰岛素分泌峰值比对照值升高了170%，而血浆磷或血浆钙浓度的显著升高与此无关。125 -(OH)2D3的降糖倾向也是剂量依赖性的。葡萄糖耐量显著改善（KG = 573 +-）。仅给药0.26 nmol (4 U) 1,25-(OH)2D3后胰岛素分泌量最大（为对照组的250%）。较高浓度的第二类固醇虽然有刺激作用，但效果较差。本研究表明，125 -(OH)2D3对维生素d缺乏大鼠体内胰岛素分泌和葡萄糖清除的增强作用（在3小时内）具有快速反应。这种降糖作用的剂量依赖性也已确立。
It has been previously demonstrated in this laboratory that vitamin D3 is essential for normal insulin secretion from the perfused rat pancreas. More recently we have shown, consistent with a physiological role for the vitamin in this process, that vitamin D-deficient rats exhibit impaired glucose clearance and insulin secretion, as monitored during iv glucose tolerance tests. Both of these parameters are significantly improved after vitamin D repletion independently of nutritional factors and the prevailing plasma calcium and phosphorus concentrations. In this present study the dose response and time course of effect of a single sc injection of the active metabolite 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on glucose tolerance and insulin secretion were investigated. The impaired glucose clearance of vitamin D-deficient rats (KG = 912 .+-. 37, where KG is a function of glucose tolerance) was markedly improved as early as 3 h after acute 1,25 (OH)2D3 (1.3 nmol;20 U) administration (KG = 676 .+-. 13), and this clearance was maintained for up to 20 h (KG = 688 .+-. 24). This improvement corresponded to enhanced glucose-induced insulin secretion. By 3 h after 1,25-(OH)2D3 substitution, the peak of insulin secretion was elevated by 170% of control values, independently of a significant increase in plasma phosphorus or plasma calcium concentrations. The hypoglycemic propensity of 1,25-(OH)2D3 was also dose dependent. Glucose tolerance was significant improved (KG = 573 .+-. 33), and insulin secretion was maximal (250% of control) after administration of only 0.26 nmol (4 U) 1,25-(OH)2D3. Higher concentrations of seco-steroid, although stimulatory, proved less effective. This study demonstrates a rapid response (within 3 h) to the potentiating action of 1,25-(OH)2D3 on in vivo insulin secretion and glucose clearance in the vitamin D-deficient rat. A dose dependence of this hypoglycemic action is also established.