Iguchi A, Miura H, Kunoh Y, Mizuno S, Uemura K, Ishiguro T, Tamagawa T, Goshima K, Sakamoto N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Life Sci. 1991;49(16):1191-6. doi: 10.1016/0024-3205(91)90567-u.
To assess the effect of chemical stimulation of the central nervous system (CNS) on ketogenesis, we injected neostigmine (5 x 10(-8)mol) into the third cerebral ventricle in normal rats fasted for 48 h and fed rats with diabetes induced by streptozotocin (STZ, 80 mg/kg). The hepatic venous plasma levels of ketone bodies (3-hydroxybutyrate and acetoacetate), free fatty acids (FFA), and glucose were measured for 120 min after the injection of neostigmine under pentobarbital anesthesia. In the normal rats, plasma glucose levels were significantly increased but neither ketone bodies nor FFA were affected by CNS stimulation with neostigmine. In contrast the plasma levels of ketone bodies and FFA were significantly increased in STZ-diabetic rats, while glucose levels remained unchanged. The intravenous infusion of somatostatin (1.0 microgram/kg/min) suppressed the increase in plasma ketone bodies following CNS stimulation in STZ-diabetic rats. These findings suggest that CNS stimulation with neostigmine may accelerate ketogenesis by promoting the lipolysis, which may be induced by glucagon, in fed diabetic rats but not in normal fasted rats.
为评估中枢神经系统(CNS)化学刺激对生酮作用的影响,我们向禁食48小时的正常大鼠以及用链脲佐菌素(STZ,80 mg/kg)诱导糖尿病的喂食大鼠的第三脑室注射新斯的明(5×10⁻⁸mol)。在戊巴比妥麻醉下注射新斯的明后120分钟,测量肝静脉血浆中酮体(3-羟基丁酸和乙酰乙酸)、游离脂肪酸(FFA)和葡萄糖的水平。在正常大鼠中,血浆葡萄糖水平显著升高,但新斯的明对中枢神经系统的刺激未影响酮体和FFA。相反,在STZ诱导的糖尿病大鼠中,酮体和FFA的血浆水平显著升高,而葡萄糖水平保持不变。静脉输注生长抑素(1.0微克/千克/分钟)可抑制STZ诱导的糖尿病大鼠中枢神经系统刺激后血浆酮体的升高。这些发现表明,新斯的明对中枢神经系统的刺激可能通过促进胰高血糖素诱导的脂肪分解来加速喂食的糖尿病大鼠而非正常禁食大鼠的生酮作用。