Effects of inducing physiological hyperglucagonemia on metabolic responses to exercise

Abstract

The purpose of the present study was to assess the effects of exogenously increasing the circulating levels of glucagon on the metabolic responses to exercise in rats. A total of six groups of rats were infused (iv) either with glucagon (20 or 50 ng x kg(-1) x min(-1)) or saline (0.9% NaCl), either in the resting state or during a bout of running exercise (45 min, 26 m x min(-1), 0% grade). Blood samples were taken at the end of the 45-min experiment. Animals infused with glucagon at 50 ng x kg(-1) x min(-1) showed significantly (P<0.01) higher mean plasma glucagon concentrations than animals infused with saline or glucagon at 20 ng x kg(-1) x min(-1). In addition, exercise resulted in significantly (P<0.05) higher mean plasma glucagon concentrations, compared to rest, in all groups. In spite of these differences in glucagon concentrations, there were no significant (P>0.05) effects of exercise and glucagon infusion on mean hepatic glycogen, plasma glucose, insulin, C-peptide, beta-hydroxybutyrate, or catecholamine concentrations. Although exercise resulted in a significant (P<0.01) increase in plasma glycerol and free fatty acid concentrations and a significant (P<0.05) decrease in glycogen in the soleus muscle, these responses were not affected by the glucagon infusion. These results suggest that the liver is non-responsive to physiological hyperglucagonemia in a short-term (45 min) exercise situation.

Long-term hyperglucagonaemia induces early metabolic and renal phenotypes of Type 2 diabetes in mice

“…This suggests that glucagon may play an important role in causing hyperglycaemia and, therefore, may contribute to increased insulin resistance in early Type 2 diabetes [2,31]. Indeed, many previous studies in humans or animals have demonstrated that glucagon administration for several hours or days was associated with or without increased fasting blood glucose levels and impaired glucose tolerance [11][12][13]. However, it has been very complicated to determine whether glucagon plays a direct role in these responses, because it is difficult to infuse glucagon to induce hyperglucagonaemia and then block its effects with its receptor antagonist [Des-His 1 -Glu 9 ]glucagon in human subjects for weeks or months.…”

“…Most previous studies have chronically infused (or injected) glucagon in humans or animals for only a few minutes, hours or days to determine the effects of glucagon on blood glucose levels, serum insulin and glucagon responses, hepatic glucose production and tissue uptake of glucose [6,[11][12][13]. None of these studies have lasted long enough to determine whether long-term hyperglucagonaemia may induce target tissue injury in a human or animal model of Type 2 diabetes.…”