Effect of Selective Denervation of the Rat Pancreas on Pancreatic Endocrine Function

Abstract

The purpose of this study was to investigate the influence of selective denervation of the rat pancreas on hormone secretion and on peripheral insulin sensitivity. Thirteen rats, 7 denervated and 6 sham operated, received an intravenous glucose challenge for 30 min. The basal plasma levels of insulin, glucagon and glucose did not differ between the two groups. An augmented insulin response to glucose was detected in the denervated group, whereas the glucagon response was unaffected. Glucose tolerance was marginally improved. Twenty-four rats, 12 denervated and 12 sham operated, received a constant infusion of glucose, insulin, epinephrine and propranolol in order to inhibit the endogenous insulin release and thus evaluate insulin sensitivity. No significant change in insulin sensitivity could be detected during our experimental conditions. We conclude that selective denervation brings about an increased insulin response to glucose, probably by interrupting a catecholaminergic negative tone on the β-cell. The sympathectomized animals did not disclose any apparent changes in peripheral insulin sensitivity.

Autonomic involvement in the permanent metabolic programming of hyperinsulinemia in the high-carbohydrate rat model

“…This would be consistent with our previous studies (46,47) showing that islets isolated from HC rats exhibited a 10-fold reduction in sensitivity to inhibition of insulin secretion by norepinephrine. Furthermore, a study of selective surgical denervation of pancreatic sympathetic innervation resulted in increased GSIS in association with impaired adrenergic stimulation of ␤-cells (38). Reduced sensitivity to adrenergic agonism in HC rats may be the result of decreased adrenergic activity at the level of the islets due to reductions in sympathetic outflow to the pancreas.…”

Antipsychotic Drug-Induced Increases in Peripheral Catecholamines are Associated With Glucose Intolerance

“…Elevated concentrations of both norepinephrine and epinephrine might therefore be expected to contribute in manifold ways to excessively elevated glucose levels, and will require future study—although some potential candidate substrates of these catecholamines, such as glucagon, are already being confirmed as presumed downstream mediators of antipsychotic-induced glucose intolerance ( Medak et al, 2019 ; Shamshoum et al, 2021 ). Physiologically, the relative importance of each of the individual catecholamines towards the drug-induced glucose dysregulation will require more targeted evaluation, involving both pharmacological and anatomical techniques [such as denervation of the pancreas ( Nilsson et al, 2001 )]. With regards to the former, in a recent study we sought to understand which of the adrenoceptors may be responsible for mediating the effects of putative increases in peripheral catecholamines on whole-body insulin resistance ( Yuen et al, 2021b ) following treatment with clozapine.…”