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.

Rat Hepatocyte Glucose Metabolism Is Affected by Caloric Restriction but not by Litter Size Reduction

“…Consistent with this idea, higher glycogen content and similar findings on liver glucose metabolism were reported in reduced-litter, calorically-restricted rats aging 90 days [31]. As rats from large litters subjected to caloric restriction after weaning also display these patterns of liver glucose metabolism [24,32,33], it can be assumed that caloric restriction had an impact on liver glucose metabolism that seems to be dependent of the prevailing nutritional condition, and not of age or litter size.…”

“…A canulla was inserted into the portal vein and another into the inferior cava vein. The surgical details are described elsewhere [24]. The perfusion fluid consisted of KH (Krebs-Henseleit) buffer (pH 7.4), heated to 37 ºC and saturated with carbogenic mixture (O 2 95%/CO 2 5%).…”

“…Glucose, pyruvate and lactate production without gluconeogenic precursors (basal productions) were used to calculate the rates of glycolysis and glycogenolysis [24].…”

Glutamine or Glutamine Dipeptide Supplementation Improves Gluconeogenesis and Liver Glycogenosis in Type 1 Diabetic Rats

“…Laparotomy was followed by cannulation of the portal vein and inferior cava vein. The surgical details are described elsewhere [22]. Euthanasia was by hypovolemic chock.…”

The Role of the Kidney in Glucose Homeostasis

“…Lactate represents the predominant gluconeogenic precursor in both organs, but regarding the aminoacids, the kidney prefers to use glutamine, whereas the liver preferentially uses alanine [19]. Insulin can suppress glucose release in both organs with almost comparable efficacy [20], whereas glucagon stimulates hepatic glucose release only [21]. Catecholamines normally have a direct effect only on renal glucose release [22], but their effect on both hepatic and renal glucose release may be indirect by increasing the quantity of gluconeogenic substrates available and by suppressing insulin secretion.…”