Expression of gluconeogenic enzymes and 11β-hydroxysteroid dehydrogenase type 1 in liver of diabetic mice after acute exercise

Abstract

Korie B Brust,1 Kathryn A Corbell,2 Layla Al-Nakkash,2 Jeganathan Ramesh Babu,3 Tom L Broderick2,4 1Department of Biomedical Sciences, College of Health Sciences, Midwestern University, Glendale, AZ, USA; 2Department of Physiology, College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA; 3Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA; 4Laboratory of Diabetes and Exercise Metabolism, Midwestern University, Glendale, AZ, USA Abstract: During acute exercise, normoglycemia is maintained by a precise match between hepatic glucose production and its peripheral utilization. This is met by a complex interplay of hepatic responses and glucose uptake by muscle. However, the effect of a single bout of exercise on hepatic gluconeogenesis, corticosterone (CORT) secretion, and glucose homeostasis in the db/db mouse model of type 2 diabetes is poorly understood. Diabetic db/db and lean control littermates were subjected to a 30 minute session of treadmill running and sacrificed either immediately after exercise or 8 hours later. Plasma glucose levels were markedly increased in db/db mice after exercise, whereas no change in glucose was observed in lean mice. Post-exercise measurements revealed that plasma CORT levels were also significantly increased in db/db mice compared to lean mice. Plasma hypothalamic corticotropin releasing hormone and pituitary adrenocorticotropic hormone levels were reciprocally decreased in both db/db and lean mice after exercise, indicating intact feedback mechanisms. Protein expression, determined by Western blot analysis, of the glucocorticoid receptor in liver was significantly increased in db/db mice subjected to prior exercise. In liver of db/db mice, a significant increase in the expression of phosphoenolpyruvate carboxykinase was noted compared to lean mice after exercise. However, no change in the expression of glucose-6-phosphatase (G6Pase) α or β was observed in db/db mice. Expression of 11β-hydroxysteroid dehydrogenase type 1 was increased significantly in db/db mice compared to lean mice after exercise. Our results show differences in plasma glucose and protein expression of gluconeogenic enzymes after acute exercise between lean and diabetic db/db mice. The db/db diabetic mouse is hyperglycemic after acute exercise. This hyperglycemic state may be explained, in part, by enhanced endogenous CORT secretion and regulated hepatic phosphoenolpyruvate carboxykinase and 11β-hydroxysteroid dehydrogenase type 1 protein expression. Keywords: diabetes, exercise, corticosterone, glucocorticoid receptor, PEPCK, 11βHSD1