sincalide and Hypoglycemia

The influence of cholecystokinin octapeptide (CCK-8) on normal and insulin-induced feeding and expression of orexigenic hypothalamic neuropeptides was investigated in male rats. CCK-8, administered during meals (4 microg/kg) or continuously (32 microg/kg over 60 min), blunted the stimulating effect of insulin (50 IU/kg) on feeding by reducing meal size (-60%; P<0.05 or -86%; P<0.0001, respectively). Rats without access to food and injected with IP insulin (50 IU/kg) showed increased hypothalamic mRNA levels of orexin (+30%; P<0.05) and melanin-concentrating hormone (+52%; P<0.05), as compared with ad libitum-fed and saline-injected control rats. Continuous IP infusion of CCK-8 (32 microg/kg) blunted these increases. Our results suggest that both orexin and melanin-concentrating hormone participate in the response to insulin hypoglycemia without food being present; these neurons may be involved in mechanisms related to insulin-induced hyperphagia. Signals triggered by peripheral CCK-8 act to decrease the expression of orexin and melanin-concentrating hormone. This may be associated with a reduction in hyperphagia.

Topics: Animals; Blood Glucose; Feeding Behavior; Hyperphagia; Hypoglycemia; Hypothalamic Hormones; Hypothalamus; Insulin; Intracellular Signaling Peptides and Proteins; Male; Melanins; Neuropeptides; Orexins; Pituitary Hormones; Rats; Rats, Sprague-Dawley; RNA, Messenger; Satiety Response; Sincalide; Time Factors

In two previous studies, postprandial pancreatic polypeptide (PP) release was inhibited when pancreatic denervation was combined with distal pancreatectomy. In contrast, postprandial PP release was unaffected by pancreatic denervation without a distal pancreatectomy. These findings suggested a role for the distal pancreas in regulation of postprandial PP release. To examine this possibility, we performed distal pancreatectomy on four mongrel dogs. Pancreatic polypeptide response to i.v. insulin (0.5 U/kg), a meal, and an infusion of cholecystokinin octapeptide (CCK-8; 50 ng/kg/h) were measured in conscious dogs before and after distal pancreatectomy. Insulin-induced hypoglycemia stimulated PP release both preoperatively (47.0 +/- 8.8 ng.[0-120]min/ml) and postoperatively (61.6 +/- 9.2 ng.[0-120]min/ml). Ingestion of a meal also evoked significant PP release preoperatively (85.8 +/- 22.1 ng.[0-180]min/ml) and postoperatively (105.8 +/- 42.2 ng.[0-180]min/ml). CCK-8 elicited only a small increase in circulating PP, which was not influenced by distal pancreatectomy. These findings demonstrate that distal pancreatectomy does not alter PP response to insulin, a meal, or CCK-8.

Topics: Animals; Blood Glucose; Dogs; Eating; Hypoglycemia; Pancreas; Pancreatic Polypeptide; Sincalide