Insulin and the Constituent Branches of the Hepatic Vagus Interact to Modulate Hypothalamic and Limbic Neuropeptide mRNA Expression Differentially

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.