Sustained Liver Glucose Release in Response to Adrenaline Can Improve Hypoglycaemic Episodes in Rats under Food Restriction Subjected to Acute Exercise

Abstract

Background. As the liver is important for blood glucose regulation, this study aimed at relating liver glucose release stimulated by glucagon and adrenaline to in vivo episodes of hypoglycaemia. Methods. The blood glucose profile during an episode of insulin-induced hypoglycaemia in exercised and nonexercised male Wistar control (GC) and food-restricted (GR, 50%) rats and liver glucose release stimulated by glucagon and adrenaline were investigated. Results. In the GR, the hypoglycaemic episodes showed severe decreases in blood glucose, persistent hypoglycaemia, and less complete glycaemic recovery. An exercise session prior to the episode of hypoglycaemia raised the basal blood glucose, reduced the magnitude of the hypoglycaemia, and improved the recovery of blood glucose. In fed animals of both groups, liver glucose release was activated by glucagon and adrenaline. In fasted GR rats, liver glycogenolysis activated by glucagon was impaired, despite a significant basal glycogenolysis, while an adrenaline-stimulated liver glucose release was recorded. Conclusions. The lack of liver response to glucagon in the GR rats could be partially responsible for the more severe episodes of hypoglycaemia observed in vivo in nonexercised animals. The preserved liver response to adrenaline can partially account for the less severe hypoglycaemia in the food-restricted animals after acute exercise.

Figure 1

Illustrative graph of liver glucose release in a fed control rat, before (basal release) and during (stimulated release) perfusion with adrenaline (1 μM). The vertical line indicates the transition from basal perfusion (KH only) to stimulated perfusion (KH with adrenaline 1 μM). The AUC of basal glucose release considered all glucose released during the 10-min interval. AUC of stimulated release considered those glucose values above the basal release during the 30-min interval.

Figure 2

Blood glucose profiles of control and food-restricted rats during insulin-induced hypoglycaemia, either without exercise ((a), groups GC and GR) or after an acute exercise session ((b), groups GCex and GRex). Insulin was i.p. injected at time 0 min and blood glucose was recorded for 300 min. Mean ± SD of 6–12 observations at each time. *P < 0.01 compared with time 0 min of the same group; ^# P < 0.01 between groups at the same time, according to Student's t-test.