Dehydroepiandrosterone sulfate and β-cell function -: Enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic β-cells
Dehydroepiandrosterone sulfate and β-cell function -: Enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic β-cells
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DOI：
10.2337/diabetes.49.12.2012
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发表时间：
2000-12-01
期刊：
影响因子：
7.7
通讯作者：
Corkey, BE
中科院分区：
文献类型：
--
作者：
Dillon, JS;Yaney, GC;Corkey, BE
施用脱氢表雄酮（DHEA）或其硫酸盐形式（DHEAS）控制糖尿病啮齿动物中的高血糖，而无需直接改变胰岛素敏感性。我表明，当在体内给大鼠或体外施用葡萄糖刺激的胰岛素分泌增强了胰岛素的分泌，而不会改变细胞胰岛素含量，胰岛素的分泌增加，从体外暴露的3天就增加了，这表明DHEAS并未直接激活激活分泌过程。 DHEA以时间依赖性方式选择性地增加了酰基COA合成酶-2和过氧化物酶体COA氧化酶的β细胞mRNA表达。尽管DHEAS是一种过氧化物酶体增生剂，但它并没有改变过氧化物酶体增殖物激活的受体（PPAR）alpha或beta的mRNA表达，也没有增强在体外的转染PPARα，beta或Gamma的活性。因此，DHEAS直接影响β细胞，以增强葡萄糖刺激的胰岛素分泌，并增加特定β细胞 - 细胞线粒体和过氧化物酶体脂质代谢酶的mRNA表达。 DHEAS对胰岛素分泌的这种影响可能有助于改善糖尿病的各种啮齿动物模型中的高血糖。
Administration of dehydroepiandrosterone (DHEA), or its sulfated form (DHEAS), controls hyperglycemia in diabetic rodents without directly altering insulin sensitivity. me show that DHEAS enhanced glucose-stimulated insulin secretion when administered in vivo to rats or in vitro to beta -cell lines, without changing cellular insulin content, insulin secretion increased from 3 days of steroid exposure in vitro, suggesting that DHEAS did not directly activate the secretory processes. DHEAS selectively increased the beta -cell mRNA expression of acyl CoA synthetase-2 and peroxisomal acyl CoA oxidase in a time-dependent manner. Although DHEAS is a peroxisomal proliferator, it did not alter the mRNA expression of peroxisomal proliferator-activated receptor (PPAR) alpha or beta, or enhance the activity of transfected PPAR alpha, beta, or gamma in vitro. Thus, DHEAS directly affected the beta -cell to enhance glucose-stimulated insulin secretion and increased the mRNA expression of specific beta -cell mitochondrial and peroxisomal lipid metabolic enzymes. This effect of DHEAS on insulin secretion may contribute to the amelioration of hyperglycemia seen in various rodent models of diabetes.