大脑中发现控制血液中的葡萄糖水平的＂开关＂

腹内侧核中含有细胞，它们是葡萄糖感受器。

　　为了了解脯氨酰肽链内切酶在大脑这部分中的作用，研究小组使用转基因小鼠，其体内这种酶的水平很低。他们发现，如果没有这种酶，小鼠血液中的葡萄糖水平就很高，会发展为糖尿病。

　　Diano及其研究小组发现，这种酶非常重要，因为它使大脑这个区域的神经元对葡萄糖很敏感。神经元感知葡萄糖水平的升高，然后告诉胰腺释放胰岛素——维持血液中葡萄糖水平稳定的激素，从而预防糖尿病。

　　Sabrina Diano，她是本文第一作者、耶鲁大学医学院产科学、妇科和生殖科学、比较医学和神经生物学系的教授，以及耶鲁综合细胞信号传导和代谢神经生物学项目成员之一。她指出：“因为内肽酶的水平较低，神经元不再对血糖水平增加敏感，无法控制胰岛素从胰腺的释放，小鼠就会发展为糖尿病。”

　　Diano说，该研究的下一步工作是，通过了解这种酶如何使神经元感知葡萄糖水平的变化，识别这种酶的靶点。她说：“如果我们能成功地做到这一点，我们就能够调节胰岛素的分泌，并能够预防和治疗2型糖尿病。”

　　这项研究是由美国国立卫生研究院和美国糖尿病协会资助支持。(来源：生物帮)

　　原文摘要：

Hypothalamic prolyl endopeptidase (PREP) regulatespancreatic insulin and glucagon secretion in mice

Jung Dae Kim, Chitoku Toda, Giuseppe D’Agostino, Caroline J. Zeiss, Ralph J. DiLeone,John D. Elsworth, Richard G. Kibbey, Owen Chan, Brandon K. Harvey, Christopher T. Richie,Mari Savolainen, Timo My?h?nnen, Jin Kwon Jeong and Sabrina Diano

　　Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report thathypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulatesglucose-induced neuronal activation. PREP knockdown mice (Prepgt/gt) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulinsecretion compared with wild-type controls. Consistent with this, central infusion of a specific PREPinhibitor, S17092, impaired glucose tolerance and decreased insulin levels in wild-type mice. Arguing further for a central mode of action of PREP, isolated pancreatic islets showed no difference in glucose-induced insulin release between Prepgt/gt and wild-type mice. Furthermore, hyperinsulinemic euglycemic clamp studies showed no difference between Prepgt/gt and wild-type control mice. Central PREP regulation of insulin and glucagon secretion appears to be mediated by the autonomic nervous system becausePrepgt/gt mice have elevated sympathetic outflow and norepinephrine levels in the pancreas, andpropranolol treatment reversed glucose intolerance in these mice. Finally, re-expression of PREP by bilateral VMH injection of adeno-associated virus–PREP reversed the glucose-intolerant phenotype of thePrepgt/gt mice. Taken together, our results unmask a previously unknown player in central regulation of glucose metabolism and pancreatic function.