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Research indicates that intestinal lipid stimulates the genetic expression of c-fos in insect locus. Experiments designed to assess the influence of intestinal lipid in the locus's nucleus of the solitary trace, paraventricular nucleus and locus ceruleus complex, are described. Results suggest that exogenous cholecystokinin-A receptors play an important role in vagal afferent pathways.

The present study was undertaken to establish in normal volunteers the alterations in [Beta]-cell responsiveness to glucose associated with a constant infusion of glucagon-like peptide-1 (GLP-1) or a pretreatment infusion for 60 min. A high-dose graded glucose infusion protocol was used to explore the dose-response relationship between glucose and insulin secretion. Studies were performed in 10 normal volunteers, and insulin secretion rates (ISR) were calculated by deconvolution of peripheral C-peptide levels by use of a two-compartmental model that utilized mean kinetic parameters. During the saline study, from 5 to 15 mM glucose, the relationship between glucose and ISR was linear. Constant GLP-1 infusion (0.4 pmol [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]) shifted the dose-response curve to the left, with an increase in the slope of this curve from 5 to 9 mM glucose from 71.0 [+ or -] 12.4 pmol [multiplied by] [min.sup.-1] [multiplied by] [mM.sup.-1] during the saline study to 241.7 [+ or -] 36.6 pmol [multiplied by] [min.sup.-1] [multiplied by] [mM.sup.-1] during the constant GLP-1 infusion (P [is less than] 0.0001). GLP-1 consistently stimulated a [is greater than] 200% increase in ISR at each 1 mM glucose interval, maintaining plasma glucose at [is less than] 10 mM (P [is less than] 0.0007). Pretreatment with GLP-1 for 60 min resulted in no significant priming of the [Beta]-cell response to glucose (P = 0.2). Insulin clearance rates were similar in all three studies at corresponding insulin levels. These studies demonstrate that physiological levels of GLP-1 stimulate glucose-induced insulin secretion in a linear manner, with a consistent increase in ISR at each 1 mM glucose interval, and that they have no independent effect on insulin clearance and no priming effect on subsequent insulin secretory response to glucose. insulin secretion; connecting peptide; priming; [Beta]-cell sensitivity