Aoki K, Kikuchi T, Mukasa K, Ito S, Nakajima A, Satoh S, Okamura A, Sekihara H
The Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Endocr J. 2000 Dec;47(6):799-804. doi: 10.1507/endocrj.47.799.
Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia of diabetic C57BL/KsJ-db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA as well as troglitazone suppresses the elevated hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities in C57BL/KsJ-db/db mice. In the present study, we evaluated the changes in mRNA of G6Pase and FBPase in db/db mice. Despite hyperinsulinemia, the G6Pase mRNA level of db/db mice was elevated as compared to their heterozygote littermate db/+m mice. In contrast, the FBPase mRNA level was not elevated in db/db mice. Administration of DHEA for two weeks significantly decreased the blood glucose level and the elevated G6Pase mRNA level in db/db mice. No significant changes were seen in the FBPase mRNA level after the administration of DHEA. Administration of troglitazone also decreased the blood glucose and G6Pase mRNA level in db/db mice although no changes were seen in the FBPase mRNA level. These results suggest that the elevation of G6Pase mRNA is important in elucidating the cause of insulin resistance, and that the G6Pase gene is at least one target for the hypoglycemic effects of DHEA as an insulin sensitizing agent in db/db mice.
已知脱氢表雄酮（DHEA）可改善肥胖且胰岛素抵抗的糖尿病C57BL/KsJ-db/db小鼠的高血糖症。在先前的一项研究中，我们报道DHEA以及曲格列酮可抑制C57BL/KsJ-db/db小鼠肝脏中升高的糖异生酶、葡萄糖-6-磷酸酶（G6Pase）和果糖-1,6-二磷酸酶（FBPase）的活性。在本研究中，我们评估了db/db小鼠中G6Pase和FBPase mRNA的变化。尽管存在高胰岛素血症，但与杂合子同窝出生的db/+m小鼠相比，db/db小鼠的G6Pase mRNA水平有所升高。相比之下，db/db小鼠的FBPase mRNA水平并未升高。给db/db小鼠连续两周施用DHEA可显著降低血糖水平以及升高的G6Pase mRNA水平。施用DHEA后，FBPase mRNA水平未见明显变化。施用曲格列酮也可降低db/db小鼠的血糖和G6Pase mRNA水平，尽管FBPase mRNA水平未见变化。这些结果表明，G6Pase mRNA的升高对于阐明胰岛素抵抗的原因很重要，并且G6Pase基因至少是DHEA作为db/db小鼠胰岛素增敏剂降血糖作用的一个靶点。
