Oversecretion of glucagon by pancreases of ventromedial hypothalamic-lesioned rats: a re-evaluation of a controversial topic.

Glucagon secretion by perfused pancreases of control and ventromedial hypothalamic-lesioned rats was studied in response to a mixture of 20 different amino-acids used at physiological or pharmacological concentrations, and under experimental conditions near to or different from physiological situations. When experimental conditions are too extreme (lack of glucose with 5 or 15 mmol/l final amino-acid concentration), there was no difference of glucagon secretion between pancreases of control and ventromedial hypothalamic-lesioned animals. However, when experimental conditions are as close as possible to those prevailing in vivo (presence of 5 mmol/l glucose with 2.5 or 5 mmol/l amino-acid concentration), pancreases from ventromedial hypothalamic-lesioned rats clearly oversecrete glucagon when compared with control rats (with 2.5 mmol/l amino-acid: controls: 7.9, ventromedialhypothalamic-lesioned: 17.1 ng/20 min, p less than 0.05; with 5 mmol/l amino-acid: controls: 12.6, ventromedialhypothalamic-lesioned: 31.0 ng/20 min, p less than 0.025). Upon extrapolating these results to a situation in vivo, this study indicates that ventromedial hypothalamic-lesioned rats secrete more glucagon than controls in response to physiological stimuli, at least at the level of the portal vein. This could explain why the lesioned rats, known to be hyperinsulinaemic, are nevertheless normoglycaemic and have increased plasma urea levels.