Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY, resulted in concomitant increased secretion of the other, probably explaining the absent effect on food intake on these experimental days. Combined blockade of GLP-1 and PYY actions increased food intake after RYGB, supporting that these hormones have a role in decreased food intake postoperatively.

Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from a-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.Patients with diabetes are characterized not only by compromised insulin secretion and action but also by elevated plasma concentrations of the 29-amino acid peptide hormone glucagon, which hitherto has been considered a pancreas-derived hormone in humans (produced in and secreted from a-cells in the islet of Langerhans) (1). In patients with diabetes, plasma concentrations of glucagon are elevated in the fasting state and fail to decrease appropriately or even increase in response to an oral glucose tolerance test (OGTT) and show exaggerated increases in response to ingestion of a mixed meal (1,2). The elevated glucagon concentrations increase the hepatic glucose production and thereby contribute significantly to the fasting and postprandial hyperglycemia characterizing patients with diabetes. The etiology behind diabetic hyperglucagonemia is still controversial. Whereas oral intake of glucose elicits a hyperglucagonemic response, intravenous glucose administration causes suppression of plasma glucagon levels (3,4). A "lighter version" of this phenomenon has also been observed in healthy individuals after ingestion of larger oral glucose loads (4). Together, these findings led us to speculate that postprandial hyperglucagonemia could be gut derived and independent of the endocrine pancreas.The notion of extrapancreatic glucagon secretion in man has been debated for years, and several studies looking at glucagon responses after total pancreatectomy in animals (5-10) and man (11-24) have been published. Overall, these investigations have reported very conflicting