Warne J P, Horneman H F, Akana S F, Foster M T, Dallman M F
Department of Physiology, University of California San Francisco, San Francisco, CA 94143, USA.
J Neuroendocrinol. 2008 Sep;20(9):1067-77. doi: 10.1111/j.1365-2826.2008.01766.x. Epub 2008 Jul 11.
Insulin and signalling through the vagus nerve act in concert to regulate metabolic homeostasis and ingestive behaviour. Our previous studies using streptozotocin (STZ)-diabetic rats have shown that hepatic branch vagotomy (HV), gastroduodenal branch vagotomy (GV) and capsaicin treatment of the common hepatic branch that selectively destroys afferent fibres (CapV), all promote lard, but not total, caloric intake to levels similar to those achieved with insulin treatment. Because hypothalamic and limbic mRNA expression of neuropeptides linked to energy balance is altered by STZ-diabetes and HV, we examined the role(s) of insulin and the common hepatic and gastroduodenal branches of the vagus nerve and hepatic afferent fibres in the regulation of these neuropeptides in rats with high, steady-state corticosterone levels. STZ-diabetic rats were prepared with osmotic minipumps containing either saline or insulin and were compared with nondiabetic counterparts: half of each group received a vagal manipulation, the other half were sham operated. Five days after surgery, rats were offered the choice of lard and chow to consume for another 5 days, when brains were collected and processed for in situ hybridisation. Paraventricular nucleus corticotrophin-releasing factor (CRF) mRNA was elevated by STZ treatment, an effect prevented by either insulin treatment or GV. By contrast, CRF mRNA expression in the central nucleus of the amygdala and bed nuclei of the stria terminalis was unaffected by STZ treatment, but HV and CapV manipulations elevated expression in the nondiabetic, but not STZ-diabetic groups. Arcuate nucleus neuropeptide Y, but not pro-opiomelanocortin, mRNA expression was elevated by STZ treatment and all vagal manipulations; however, exogenous insulin treatment failed to prevent this, in keeping with their previously documented elevated caloric intake. These results strongly suggest that the gastroduodenal branch and hepatic branch proper, which merge to form the common hepatic branch, differentially interact with prevailing insulin levels to regulate hypothalamic and limbic neuropeptide mRNA expression.
胰岛素和通过迷走神经的信号传导协同作用，以调节代谢稳态和摄食行为。我们之前使用链脲佐菌素（STZ）诱导的糖尿病大鼠进行的研究表明，肝支迷走神经切断术（HV）、胃十二指肠支迷走神经切断术（GV）以及用辣椒素处理选择性破坏传入纤维的肝总支（CapV），均能促进猪油（而非总热量）的摄入，使其达到与胰岛素治疗相似的水平。由于与能量平衡相关的神经肽的下丘脑和边缘系统mRNA表达会因STZ诱导的糖尿病和HV而改变，我们研究了胰岛素、迷走神经的肝总支和胃十二指肠支以及肝传入纤维在稳态皮质酮水平较高的大鼠中对这些神经肽调节的作用。给STZ诱导的糖尿病大鼠植入含生理盐水或胰岛素的渗透微型泵，并与非糖尿病大鼠进行比较：每组一半接受迷走神经操作，另一半进行假手术。术后5天，给大鼠提供猪油和食物供其选择再食用5天，之后收集大脑并进行原位杂交处理。STZ处理可使室旁核促肾上腺皮质激素释放因子（CRF）mRNA升高，胰岛素治疗或GV可预防此效应。相比之下，杏仁核中央核和终纹床核中的CRF mRNA表达不受STZ处理影响，但HV和CapV操作在非糖尿病组而非STZ糖尿病组中升高了表达。STZ处理和所有迷走神经操作均可使弓状核神经肽Y（而非阿黑皮素原）mRNA表达升高；然而，外源性胰岛素治疗未能预防此现象，这与之前记录的它们热量摄入增加一致。这些结果强烈表明，合并形成肝总支的胃十二指肠支和肝支本身与当前胰岛素水平存在差异相互作用，以调节下丘脑和边缘系统神经肽mRNA表达。
