Obici Silvana, Zhang Bei B, Karkanias George, Rossetti Luciano
Department of Medicine, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Nat Med. 2002 Dec;8(12):1376-82. doi: 10.1038/nm1202-798. Epub 2002 Nov 11.
Circulating insulin inhibits endogenous glucose production. Here we report that bidirectional changes in hypothalamic insulin signaling affect glucose production. The infusion of either insulin or a small-molecule insulin mimetic in the third cerebral ventricle suppressed glucose production independent of circulating levels of insulin and of other glucoregulatory hormones. Conversely, central antagonism of insulin signaling impaired the ability of circulating insulin to inhibit glucose production. Finally, third-cerebral-ventricle administration of inhibitors of ATP-sensitive potassium channels, but not of antagonists of the central melanocortin receptors, also blunted the effect of hyperinsulinemia on glucose production. These results reveal a new site of action of insulin on glucose production and suggest that hypothalamic insulin resistance can contribute to hyperglycemia in type 2 diabetes mellitus.
循环胰岛素可抑制内源性葡萄糖生成。在此我们报告，下丘脑胰岛素信号的双向变化会影响葡萄糖生成。向第三脑室注入胰岛素或小分子胰岛素模拟物可抑制葡萄糖生成，且这一作用与循环胰岛素水平及其他葡萄糖调节激素无关。相反，胰岛素信号的中枢拮抗作用会损害循环胰岛素抑制葡萄糖生成的能力。最后，向第三脑室注射ATP敏感性钾通道抑制剂而非中枢促黑素皮质素受体拮抗剂，也会减弱高胰岛素血症对葡萄糖生成的影响。这些结果揭示了胰岛素在葡萄糖生成方面的一个新作用位点，并表明下丘脑胰岛素抵抗可能导致2型糖尿病患者出现高血糖。
