Chen Y, Uemura K, Yoshioka S, Surina-Baumgartner D M, Miura H, Tamagawa T, Hotta N, Iguchi A
Department of Geriatric Medicine, Nagoya University School of Medicine, Japan.
J Auton Nerv Syst. 1998 Jun 30;71(1):10-7. doi: 10.1016/s0165-1838(98)00055-1.
To investigate whether insulin secretion induced by stimulation of the vagus nerve is preserved or impaired in Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, we injected 10(-8) mol of thyrotropin-releasing hormone (TRH) into the third cerebral ventricle and determined the serum level of insulin in the unanesthetized, unrestrained rats. Intracerebroventricular (i.c.v.) injection increased the serum levels of glucose and insulin in both OLETF and Long-Evans-Tokushima-Otsuka (LETO) rats, a nondiabetic control strain, at 8-12 weeks of age. At 24-28 weeks of age, the increased level of glucose in OLETF rats was comparable to LETO rats but that of insulin was lower than control after the i.c.v. injection of TRH. Pretreatment with i.v. atropine had no significant effect on such hyperglycemia. However, the increases in the serum levels of insulin were suppressed in both OLETF and LETO rats. The plasma levels of epinephrine, norepinephrine, and glucagon rose significantly after TRH. There was no significant difference in the levels of any hormones between the two groups. In OLETF rats at 24-28 weeks of age, i.v. glucose load induced significantly higher serum levels of glucose and insulin than LETO rats. The results suggest that the vagus nerve-mediated insulin secretion is impaired in OLETF rats, similar to an autonomic diabetic neuropathy in the early stage of diabetes. This impairment may play some role in deteriorating glucose tolerance in this spontaneously developed diabetes model.
为了研究在大冢-朗-伊文斯-德岛肥胖（OLETF）大鼠中，迷走神经刺激诱导的胰岛素分泌是保持正常还是受损，我们将10(-8)摩尔促甲状腺激素释放激素（TRH）注入第三脑室，并测定未麻醉、未束缚大鼠的血清胰岛素水平。脑室内（i.c.v.）注射使8-12周龄的OLETF大鼠和非糖尿病对照品系大冢-朗-伊文斯-德岛（LETO）大鼠的血清葡萄糖和胰岛素水平均升高。在24-28周龄时，OLETF大鼠的葡萄糖升高水平与LETO大鼠相当，但脑室内注射TRH后胰岛素升高水平低于对照组。静脉注射阿托品预处理对这种高血糖症无显著影响。然而，OLETF大鼠和LETO大鼠的血清胰岛素水平升高均受到抑制。TRH后肾上腺素、去甲肾上腺素和胰高血糖素的血浆水平显著升高。两组之间任何激素水平均无显著差异。在24-28周龄的OLETF大鼠中，静脉注射葡萄糖负荷诱导的血清葡萄糖和胰岛素水平显著高于LETO大鼠。结果表明，OLETF大鼠中迷走神经介导的胰岛素分泌受损，类似于糖尿病早期的自主神经病变。这种损伤可能在这个自发形成的糖尿病模型中糖耐量恶化中起一定作用。
