The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.

The effect of acute i.v. administration of 2.5 mg metoclopramide (MCP), an antidopaminergic agent with low serotoninergic activity, on blood insulin and glucose concentrations was studied in 9 healthy men. MCP was able to significantly decrease basal serum insulin levels (from 6.8 +/- 1.1 to 4.3 +/- 0.7 microU/ml in 120 min; p less than 0.025) with a parallel elevation in blood glucose (from 72.5 +/- 1.1 to 82.6 +/- 2.5 mg/dl in 120 min; p less than 0.01). These findings, which were not observed after placebo, and appeared not to be explained by the spontaneous occurrence of physiological oscillations of insulin and glucose plasma levels, are consistent with similar effects observed after administration of other antidopaminergic agents and with the stimulatory activity on insulin and glucagon release described during dopamine infusion in man.