Animal experiments have demonstrated that incremental increases in insulin release are associated with significantly increased glucose utilization. Such incremental insulin release coincides with ingestion and occurs during the first few minutes of a meal. Several mechanisms have been proposed for this """"""""cephalic phase insulin release"""""""" which has been considered to be vagal or parasympathetic neural in origin. This research is designed to demonstrate the existence of these metabolic effects in humans and to elucidate the mechanisms in normal human volunteers. What factor or factors are responsible for the increased glucose metabolism seen during ingestion as compared to intravenous or intragastric delivery of the same glucose load? Dr. Teff has succeeded in demonstrating consistently and reproducibly in humans. She now proposes to use the method to study glucose, insulin, connecting peptide (C-peptide) and glucagon kinetics in a series of experiments using modified sham feeding (MSF; """"""""chew-and-spit""""""""), nasogastric intubation bypassing conventional chemosensory stimulation, and intravenous infusion, bypassing gastrointestinal afferent stimulation, with and without pharmacological blockade of parasympathetic nerve activity (using atropine). To tease out the possible independent role of insulin, the principal investigator will pharmacologically block the PNS with atropine while infusing physiological doses of insulin mimicking levels elicited by cephalic insulin release. Timing of insulin infusion is crucial for this experiment as has been recognized by the principal investigator. Ingestion of glucose will be compared to infusion of glucose with and without atropine to determine whether the normal incremental increase in insulin can be blocked and if so, the degree of blockade. This would demonstrate the relative contribution of neural and humoral/hormonal/peptidergic factors.
| Havel, P J; Townsend, R; Chaump, L et al. (1999) High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes 48:334-41 |
| Teff, K L; Alavi, A; Chen, J et al. (1999) Muscarinic blockade inhibits gastric emptying of mixed-nutrient meal: effects of weight and gender. Am J Physiol 276:R707-14 |
