Effects of muscarinic blockade on insulin secretion and on glucose‐induced thermogenesis in lean and obese human subjects

Abstract

To determine whether hyperinsulinaemia of human obesity is dependent on the activity of the parasympathetic nervous system, and whether activation of the parasympathetic nervous system plays a role in glucose-induced thermogenesis, the metabolic effect of a continuous intravenous glucose infusion [44.4 mumol kg-1 body weight (bw) min-1] with or without atropine infusion was assessed in 11 obese patients and 10 lean controls. Compared with lean controls, obese patients had increased basal and glucose-stimulated plasma insulin and C-peptide concentrations and increased plasma glucose concentrations during glucose infusion. Glucose oxidation during i.v. glucose was lower in obese patients than in lean controls. Glucose-induced thermogenesis was similar in obese patients and in lean controls. Atropine infusion did not affect basal plasma glucose, insulin or free fatty acid concentrations nor glucose-stimulated plasma glucose, insulin, C-peptide, glucagon or free fatty acid concentrations in both groups of subjects. Glucose and lipid oxidation rates and glucose-induced thermogenesis were also unaffected by atropine administration. It is concluded that (1) glucose-stimulated hyperinsulinaemia in human obesity is not dependent on a hyperactivity of the parasympathetic nervous system, which indicates that human obesity is different from most animal models of obesity; (2) glucose-induced thermogenesis is similar in obese and lean subjects when a similar load of glucose is administered; (3) inhibition of the parasympathetic nervous system does not affect the thermic effect of i.v. glucose.

The Cephalic Insulin Response to Meal Ingestion in Humans Is Dependent on Both Cholinergic and Noncholinergic Mechanisms and Is Important for Postprandial Glycemia

“…This consideration is based on a previous study in healthy women in which infusions of trimethaphan or atropine after no meal was ingested resulted in no changes in baseline insulin or glucose levels (B.A., unpublished observations). Similarly, it has been shown previously that atropine does not affect baseline insulin or glucose levels in humans (10,36,37). This consideration is also supported by the absence of any change in basal insulin and glucose levels during the 15 or 10 min preceding meal ingestion, but after administration of trimethaphan or atropine in the present study.…”

Early phase insulin infusion and muscarinic blockade in obese and lean subjects

“…In the subset of obese subjects, fasting leptin levels were also significantly elevated, but no significant differences were found between the two populations for PP. During the 30-min period before meal ingestion, atropine administration significantly lowered plasma glucagon in both the lean and obese subjects but had no effect on basal levels of plasma insulin or glucose (Table 2), supporting findings by other investigators (7,41).…”

“…The increase in preabsorptive insulin is thought to be a reflection of increased PNS activity, exhibited in many animal models of obesity (22,31,39). However, in humans there is little evidence supporting an increase in PNS activity at the level of the pancreas (24,41). Furthermore, we (53) and other investigators (46) have suggested that increases in preabsorptive insulin release in obesity are merely a reflection of increased basal insulin levels.…”

“…In humans, experiments investigating the role of the PNS in glucose metabolism report conflicting results. Atropine has been shown to inhibit insulin release in some (5,15) but not all (23,41) studies. Discordant results are partially a result of the different routes of nutrient administration.…”

The role of efferent cholinergic transmission for the insulinotropic and glucagonostatic effects of GLP-1

“…However, very limited data exist to support the hypothesis of a neural mechanism underlying the effects of GLP-1 in humans. In humans, a selective block of afferent vagal transmission is not easily accomplished, but efferent activity may be blocked by using either a ganglionic blocker or atropine (2,4,44,46). The present study was designed to investigate the role of efferent vagal, muscarinic activity for the insulinotropic and glucagonostatic effects of GLP-1.…”