Role of Corticosterone and Expression of 11ß-Hydroxysteroid Dehydrogenase Type 1 in Liver on Post-Exercise Hyperglycemia in the Obese Diabetic Mouse

Abstract

Exercise training is recommended for the treatment of diabetes mellitus for the benefits on blood glucose control, obesity, and cardiometabolic risk factors. Exercise decreases adipose tissue content and fasting blood glucose, and improves insulin sensitivity. The diet-induced or spontaneous insulin-resistant obese and diabetic rat models to study the effects of exercise training have been widely used because of the favorable outcome on glucose homeostasis. However, the effects of exercise on overall glucose control in the db/db mouse of diabetes remain unclear. The db/db mouse resembles the human condition of type 2 diabetes mellitus and is characterized by hyperleptinemia, hyperglycemia and obesity resulting from a mutation in the leptin receptor gene. The db/db mouse exhibits hypercorticosteronemia, which is also reflective of the human condition. Depending on the exercise training regimen, glucose metabolism is either slightly improved or is further compromised. In this communication, the effects of voluntary and forced treadmill exercise running on glucose control in the db/db mouse are mentioned. In addition, the effects of acute exercise on glucose homeostasis are discussed, along with potential mechanisms explaining the post-exercise hyperglycemia seen in the db/db mouse. to elicit a greater stimulus based on intensity and training volume (3-fold higher than voluntary running), and with expectations that this would decrease both the obesity and hyperglycemia in db/db mice. After 12 weeks of voluntary wheel running, body weight dropped by ~5% while fasting blood glucose levels decreased by ~21% compared to sedentary db/db mice (Figures 1 and 2). Forced treadmill running however, did not overcome the disturbances associated with the db/db mouse. In fact, both body weight and blood glucose were increased by ~8-10% and mice remained insulin resistant (Figure 3). When the data was expressed as percent change from the onset of exercise training, the greatest changes in body weight and fasting blood glucose levels were observed in db/db mice subjected to treadmill running (Table 1). Based on these observations, increasing the training volume by altering intensity does not always correlate with greater weight loss and improved metabolic control in the db/db mouse. Results from earlier studies in obesity models have suggested that an exaggerated stress response associated with forced treadmill exercise could explain these unfavorable changes in the db/db mouse. Daily short-term exposure to stress can induce adrenal gland hypertrophy and disruption the consequences of exercise training on cardiovascular and metabolic outcome in the diabetic state [11][12][13][14][15]. For these reasons, the use of these particular models is justified in exercise studies and for translationalbased application in the treatment of humans with this metabolic disorder. However, in recent years, the use of the db/db mouse model of diabetes to investigate the impact of exercise training has gained popularity. Yet, since the early...