Postprandial GLP-1, norepinephrine, and reactive hypoglycemia in dumping syndrome

Abstract

Rapid gastric emptying and exaggerated plasma concentrations of the insulinotropic hormone GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients. We suspected that the plasma volume drop associated with rapid gastric emptying (early dumping) would be accompanied by elevated plasma concentrations of norepinephrine. In order to study any relationship between postprandial norepinephrine, the enteroinsular axis, and plasma glucose, twelve patients with dumping syndrome and nine controls were studied. The plasma concentrations of norepinephrine, GLP-1, GIP, glucagon, insulin, and glucose were measured following a 1.5 g/kg lean body mass glucose meal. The early (0-30 min) integrated norepinephrine concentration was significantly higher in dumpers (22.1 ± 3.8 nmol/ml/min) compared to controls (14.7 ± 3.1 nmol/ml/min; P < 0.001) and correlated closely with the postprandial hematocrit increment (r = 0.71; P < 0.05). Early immunoreactivities of GLP-1, GIP, and glucagon peaked 30 rain after glucose ingestion and were significantly higher in dumpers. Insulin peaked after 60 min and correlated with early GLP-1. In 11 of the patients glucose fell below baseline after a median interval of 120 min. Glucose at 120 min, when most of the nadirs occurred was lowest in patients with high early GLP-1 concentrations (r = 0.78; P < 0.001). Gel filtration chromatography of the dumpers' plasma revealed that pancreatic glucagon was detectable at time 0 and after 20 min, but not after 120 min. It is concluded that in dumpers pancreatic glucagon is augmented in the early postprandial period, probably through stimulation by catecholamines. At 120 min, when most of the hypoglycemias are encountered, pancreatic glucagon is no longer detectable, probably through inhibition by GLP-1.