Mundinger Thomas O, Mei Qi, Figlewicz Dianne P, Lernmark Ake, Taborsky Gerald J
Division of Endocrinology and Metabolism, Veterans Affairs Puget Sound Health Care System, and Department of Medicine, University of Washington, Seattle, USA.
Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E1047-54. doi: 10.1152/ajpendo.00136.2003. Epub 2003 Jul 22.
We investigated the functional impact of a recently described islet-specific loss of sympathetic nerves that occurs soon after the autoimmune destruction of beta-cells in the BB diabetic rat (35). We found that the portal venous (PV) glucagon response to sympathetic nerve stimulation (SNS) was markedly impaired in newly diabetic BB rats (BB D). We next found a normal glucagon response to intravenous epinephrine in BB D, eliminating the possibility of a generalized secretory defect of the BB D alpha-cell as the mediator of the impaired glucagon response to SNS. We then sought to determine whether the glucagon impairment to SNS in BB D was due solely to their loss of islet sympathetic nerve terminals or whether other effects of autoimmune diabetes contributed. We therefore reproduced, in nondiabetic Wistar rats, an islet nerve terminal loss similar to that in BB D with systemic administration of the sympathetic neurotoxin 6-hydroxydopamine. The impairment of the glucagon response to SNS in these chemically denervated, nondiabetic rats was similar to that in the spontaneously denervated BB D. We conclude that the early sympathetic islet neuropathy of BB D causes a functional defect of the sympathetic pathway to the alpha-cell that can, by itself, account for the impaired glucagon response to postganglionic SNS.
我们研究了最近描述的胰岛特异性交感神经缺失的功能影响，这种缺失发生在BB糖尿病大鼠β细胞自身免疫性破坏后不久（35）。我们发现，新患糖尿病的BB大鼠（BB D）门静脉（PV）胰高血糖素对交感神经刺激（SNS）的反应明显受损。接下来我们发现BB D对静脉注射肾上腺素的胰高血糖素反应正常，排除了BB D α细胞普遍存在分泌缺陷作为胰高血糖素对SNS反应受损介导因素的可能性。然后我们试图确定BB D中胰高血糖素对SNS的损伤是否仅由于胰岛交感神经末梢的丧失，或者自身免疫性糖尿病的其他影响是否也有作用。因此，我们在非糖尿病的Wistar大鼠中，通过全身给予交感神经毒素6-羟基多巴胺，重现了与BB D中相似的胰岛神经末梢丧失。这些化学去神经的非糖尿病大鼠中胰高血糖素对SNS的反应损伤与自发去神经的BB D相似。我们得出结论，BB D早期的交感神经胰岛神经病变导致了通向α细胞的交感神经通路的功能缺陷，这本身就可以解释胰高血糖素对节后SNS反应受损的原因。
