Boyle P J, Liggett S B, Shah S D, Cryer P E
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
J Clin Invest. 1988 Aug;82(2):445-9. doi: 10.1172/JCI113617.
To explore the potential role of the parasympathetic nervous system in human glucoregulatory physiology, responses to the muscarinic cholinergic agonist bethanechol (5.0 mg s.c.) and antagonist atropine (1.0 mg i.v.) were measured in normal humans. There were no changes in the plasma glucose concentration or rates of glucose production or utilization following atropine administration. After bethanechol administration there were no changes in the plasma glucose concentration or fluxes despite increments in plasma glucagon (75 +/- 7 to 103 +/- 10 pg/ml, P less than 0.02). There were no changes in insulin or C-peptide levels. To test the hypothesis that direct muscarinic inhibition of glucose production was offset by an indirect action of the agonist, specifically increased glucagon secretion with consequent stimulation of glucose production, bethanechol was administered while glucagon levels were held constant with the islet clamp technique (somatostatin infusion with insulin, glucagon and growth hormone replacement at fixed rates). Under that condition the muscarinic agonist induced a 25% decrement in the plasma glucose concentration (101 +/- 8 to 75 +/- 8 mg/dl, P less than 0.05). When compared with separate clamp control studies (with placebo rather than bethanechol injection) both the rate of glucose production and the glucose concentration were reduced (P less than 0.05) following bethanechol injection; the rate of glucose utilization was unaltered. Thus, we conclude: Withdrawal of parasympathetic tone does not appear to be an important glucoregulatory process in humans. Direct muscarinic cholinergic inhibition of hepatic glucose production occurs in humans but during generalized muscarinic activation this is offset by an indirect muscarinic action, increased glucagon secretion with consequent stimulation of glucose production. Thus, particularly if regional neuronal firing occurs, the parasympathetic nervous system may play an important role in human glucoregulatory physiology.
为探究副交感神经系统在人体糖调节生理中的潜在作用，对正常人体测量了其对毒蕈碱型胆碱能激动剂氨甲酰甲胆碱（5.0毫克，皮下注射）和拮抗剂阿托品（1.0毫克，静脉注射）的反应。注射阿托品后，血浆葡萄糖浓度、葡萄糖生成率或利用率均无变化。注射氨甲酰甲胆碱后，尽管血浆胰高血糖素升高（从75±7皮克/毫升增至103±10皮克/毫升，P＜0.02），但血浆葡萄糖浓度和通量均无变化。胰岛素或C肽水平也无变化。为检验激动剂的间接作用（特别是胰高血糖素分泌增加，进而刺激葡萄糖生成）抵消了毒蕈碱对葡萄糖生成的直接抑制这一假说，采用胰岛钳夹技术（以固定速率输注生长抑素并补充胰岛素、胰高血糖素和生长激素）使胰高血糖素水平保持恒定时，注射氨甲酰甲胆碱。在此条件下，毒蕈碱激动剂使血浆葡萄糖浓度降低了25%（从101±8毫克/分升降至75±8毫克/分升，P＜0.05）。与单独的钳夹对照研究（注射安慰剂而非氨甲酰甲胆碱）相比，注射氨甲酰甲胆碱后葡萄糖生成率和葡萄糖浓度均降低（P＜0.05）；葡萄糖利用率未改变。因此，我们得出结论：在人体中，副交感神经张力的减退似乎并非重要的糖调节过程。在人体中，毒蕈碱型胆碱能直接抑制肝脏葡萄糖生成，但在全身性毒蕈碱激活过程中，这一作用被毒蕈碱的间接作用（胰高血糖素分泌增加，进而刺激葡萄糖生成）所抵消。因此，特别是如果发生局部神经元放电，副交感神经系统可能在人体糖调节生理中发挥重要作用。
