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

Abstract

We studied the mechanisms and physiological relevance of the cephalic insulin response to meal ingestion in 12 healthy women (age 63 ؎ 0.4 years; BMI 27.7 ؎ 1.7 kg/m 2 ). The ganglionic antagonist, trimethaphan, which impairs neurotransmission across parasympathetic and sympathetic autonomic ganglia, or atropine or saline was given intravenously during the first 15 min after ingestion of a standard meal (350 kcal). During saline infusion, insulin levels increased during the first 10 min after meal ingestion, whereas the first increase in glucose was evident at 15 min. The preabsorptive 10-min insulin response was reduced by 73 ؎ 11% by trimethaphan (P ‫؍‬ 0.009), accompanied by impaired reduction of glucose levels from 25 to 60 min after meal ingestion (⌬glucose ‫؍‬ -1.27 ؎ 0.5 [with saline] vs. 0.1 ؎ 0.4 mmol/l [with trimethaphan]; P ‫؍‬ 0.008). This reduction at 25-60 min in glucose levels correlated significantly to the 10-min insulin response (r ‫؍‬ 0.65, P ‫؍‬ 0.024). The 10-min insulin response to meal ingestion was also reduced by atropine, but only by 20 ؎ 9% (P ‫؍‬ 0.045), which was lower than the reduction with trimethaphan (P ‫؍‬ 0.004). The preabsorptive insulin response was not accompanied by any increase in circulating levels of gastric inhibitory polypeptide (GIP) or glucagon-like peptide 1 (GLP-1). In conclusion, 1) the early preabsorptive insulin response to meal ingestion in humans can be largely attributed to autonomic activation mediated by noncholinergic and cholinergic mechanisms, 2) this cephalic insulin response is required for a normal postprandial glucose tolerance, and 3) GIP and GLP-1 do not contribute to the preabsorptive cephalic phase insulin response to meal ingestion.

Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans

“…This interrupts neural transmission across the ganglia. We have previously used this approach to study the contribution of autonomic mechanisms to counter regulatory responses to hypoglycaemia [21] and to the cephalic phase of insulin secretion after meal ingestion [22]. The main finding in the present study is that when infusing trimethaphan after the 3 days of dexamethasone treatment, the augmented arginineinduced insulin secretion was impaired, both at low, medium and high glucose levels.…”

“…In this model, insulin resistance is experimentally induced by a 3 day treatment with dexamethasone. Trimethaphan impairs neurotransmission across the autonomic ganglia and in the adrenal medulla [20] and has been used previously to evaluate autonomic regulation of islet function [21,22]. The glucose-dependent argininestimulation test, which allows for estimation of baseline as well as glucose-augmented and maximal insulin secretion, has also been used in previous studies [23,24].…”

Anticipatory physiological regulation in feeding biology: Cephalic phase responses

“…Although the magnitude of the cephalic phase insulin response is lower than the postprandial response, it appears to have significant physiological effects (Ahren and Holst, 2001). The cephalic phase insulin response has been shown in rats to be sufficient to increase lipoprotein lipase activity in adipose tissue and decrease it in muscle (Picard et al, 1999).…”

“…The cephalic phase insulin response has been shown in rats to be sufficient to increase lipoprotein lipase activity in adipose tissue and decrease it in muscle (Picard et al, 1999). Preventing the cephalic insulin phase response, for example through infusion of trimethaphan, which inhibits neurotransmission across autonomic ganglia results in both significantly higher peak blood glucose concentration and impaired reduction of glucose within the first hour post prandial ( Figure 3; Ahren and Holst, 2001),. Thus the absence of a cephalic phase insulin response compromises glucose control and can even lead to hyperinsulinemia (Berthoud et al, 1980).…”

“…Insulin levels were higher in the saline infused women compared to the trimethaphan infused women at minutes 3, 7 and 15 after beginning the meal (indicated by *). Data from Ahren and Holst, 2001. Cephalic phase insulin response to the ingestion of different volumes of 0.15% sodiumsaccharin solution in rats.…”