Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia
Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia
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DOI：
10.2337/db07-0837
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发表时间：
2008-02-01
期刊：
影响因子：
7.7
通讯作者：
Sherwin, Robert S.
中科院分区：
文献类型：
--
作者：
McCrimmon, Rory J.;Shaw, Margaret;Sherwin, Robert S.
在啮齿动物模型中的AMP激活的蛋白激酶（AMPK）在腹内侧下丘脑（VMH）在葡萄糖感知过程中的潜在作用，在体内检查hypoglycaemia.RESEARCH设计和方法，使用基因沉默技术选择性下调AMPK在VMH，一个关键的下丘脑葡萄糖感知区域，我们证明了AMPK在低血糖检测的关键作用。体内高胰岛素-低血糖（50 mg dl（-1））钳夹研究在清醒的、长期插管的Sprague-Dawley大鼠中进行，所述大鼠已经用表达AMPK α短发夹RNA的腺相关病毒（AAV）载体双侧显微注射到VMH。VMH AMPK下调导致对急性低血糖的胰高血糖素（类似于60%）和肾上腺素（类似于40%）反应受到抑制。大鼠VMH AMPK下调也需要更多的外源性葡萄糖，以维持低血糖高原，并表现出显着减少内源性葡萄糖的生产和全身葡萄糖uptake.CONCLUSIONs-We的结论，AMPK在VMH起着关键作用，在检测急性低血糖和启动的葡萄糖反调节反应。
OBJECTIVE-To examine in vivo in a rodent model the potential role of AMP-activated protein kinase (AMPK) within the ventromedial hypothalamus (VMH) in glucose sensing during hypoglycemia.RESEARCH DESIGN AND METHODS-Using gene silencing technology to selectively downregulate AMPK in the VMH, a key hypothalamic glucose-sensing region, we demonstrate a key role for AMPK in the detection of hypoglycemia. In vivo hyperinsulinemic-hypoglycemic (50 mg dl(-1)) clamp studies were performed in awake, chronically catheterized Sprague-Dawley rats that had been microinjected bilaterally to the VMH with an adeno-associated viral (AAV) vector expressing a short hairpin RNA for AMPK alpha.RESULTS-In comparison with control studies, VMH AMPK downregulation resulted in suppressed glucagon (similar to 60%) and epinephrine (similar to 40%) responses to acute hypoglycemia. Rats with VMH AMPK downregulation also required more exogenous glucose to maintain the hypoglycemia plateau and showed significant reductions in endogenous glucose production and whole-body glucose uptake.CONCLUSIONS-We conclude that AMPK in the VMH plays a key role in the detection of acute hypoglycemia and initiation of the glucose counterregulatory response.