Deletion of theMen1Gene Prevents Streptozotocin-Induced Hyperglycemia in Mice

[摘要] Diabetes ultimately results from an inadequate number of functional beta cells in the islets of Langerhans. Enhancing proliferation of functional endogenous beta cells to treat diabetes remains underexplored. Here, we report that excision of theMen1gene, whose loss-of-function mutation leads to inherited multiple endocrine neoplasia type 1 (MEN1), rendered resistant to streptozotocin-induced hyperglycemia in a tamoxifen-inducible and temporally controlledMen1excision mouse model as well as in a tissue-specificMen1excision mousemodel.Men1excision prevented mice from streptozotocin-induced hyperglycemia mainly through increasing the number of functional beta cells. BrdU incorporation by beta cells, islet size, and circulating insulin levels were significantly increased inMen1-excised mice. Membrane localization of glucose transporter 2 was largely preserved inMen1-excised beta cells, but not inMen1-expressing beta cells. Our findings suggest that repression of menin, a protein encoded by theMen1gene, might be a valuable means to maintain or increase the number of functional endogenous beta cells to prevent or ameliorate diabetes.

[学科分类] 内分泌与代谢学