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首页> 外文期刊>Endocrinology >Essentiality of portal vein receptors in hypoglycemic counterregulation: Direct proof via denervation in male canines
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Essentiality of portal vein receptors in hypoglycemic counterregulation: Direct proof via denervation in male canines

机译：门静脉受体在降血糖反调节中的必要性：通过雄性神经的去神经作用直接证明

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摘要

A major issue of in the treatment of diabetes is the risk of hypoglycemia. Hypoglycemia is detected both centrally and peripherally in the porto-hepatic area. The portal locus for hypoglycemic detection was originally described using the "local irrigation of the liver" approach in a canine model. Further work using portal vein denervation (DEN) in a rodent model characterized portal hypoglycemic sensing in detail. However, recent controversy about the relevance of rodent findings to large animals andhumansprompted us to investigate the effect of portalDENonthe hypoglycemic response in the canine, a species with multiple similarities to human glucose homeostasis. Hypoglycemic hyperinsulinemic clamps were performed in male canines, before (PRE) and after (POST) portal vein DEN or sham surgery (CON, control). Insulin (30 pmol/kg·min) and glucose (variable) were infused to slowly decrease systemic glycemia to 50 mg/dL over 160 minutes. The average plasma glucose during clamp steady state was: 2.9 ± 0.1 mmol DEN-PRE, 2.9 ± 0.2 mmol DEN-POST, 2.9 ± 0.1 mmol CON-PRE, and 2.8 ± 0.0 mmol CON-POST. There were no significant differences in plasma insulin between DEN and CON, PRE and POST experiments. The epinephrine response to hypoglycemia was reduced by 62% in DEN but not in CON. Steady-state cortisol was 46% lower after DEN but not after CON. Our study shows, in a large animal model, that surgical disconnection of the portal vein from the afferent pathway of the hypoglycemic counterregulatory circuitry results in a substantial suppression of the epinephrine response and a significant impact on cortisol response. These findings directly demonstrate an essential role for the portal vein in sensing hypoglycemia and relating glycemic information to the central nervous system.
机译：糖尿病治疗中的主要问题是低血糖的风险。在门肝区域中枢和外周均检测到低血糖症。最初在犬模型中使用“肝脏局部冲洗”方法描述了用于降血糖检测的门脉基因座。在啮齿动物模型中使用门静脉去神经支配（DEN）进行的进一步工作详细描述了门静脉降血糖的感觉。但是，最近关于啮齿动物发现与大型动物和人类的相关性的争议促使我们研究了PortalDEN对犬中降血糖反应的影响，犬与人葡萄糖体内稳态具有多种相似性。在雄性犬中，在门静脉DEN或假手术（CON，对照）之前（PRE）和之后（POST）进行降血糖高胰岛素钳夹。输注胰岛素（30 pmol / kg·min）和葡萄糖（可变）可在160分钟内将全身血糖缓慢降至50 mg / dL。钳夹稳态期间的平均血浆葡萄糖为：2.9±0.1 mmol DEN-PRE，2.9±0.2 mmol DEN-POST，2.9±0.1 mmol CON-PRE和2.8±0.0 mmol CON-POST。 DEN和CON，PRE和POST实验之间的血浆胰岛素无明显差异。肾上腺素对低血糖的反应在DEN中降低了62％，但在CON中未降低。 DEN后，稳态皮质醇降低了46％，但CON后没有降低。我们的研究显示，在大型动物模型中，门静脉与降血糖反调节电路的传入途径的手术断开会导致肾上腺素反应的显着抑制和对皮质醇反应的显着影响。这些发现直接证明了门静脉在感知低血糖以及将血糖信息与中枢神经系统相关方面的重要作用。

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