Attenuation of type 2 diabetes mellitus in the male Zucker diabetic fatty rat: the effects of stress and non-volitional exercise

To date, a limited number of studies have investigated the effects of exercise on the maintenance of endocrine pancreatic adaptations to worsening insulin resistance. In particular, the roles of stress hormones that are associated with commonly used forced-exercise paradigms are not fully explained. To examine the effects of exercise per se in ameliorating pancreatic decompensation over time, we investigated the role of forced swimming and sham exercise stress on the development of type 2 diabetes mellitus in the Zucker diabetic fatty (ZDF) rat. Thirty-two male ZDF rats were obtained at 5 weeks of age and all went through a 1-week acclimatization period. They were then divided into 4 groups: basal (euthanized at 6 weeks of age), exercise (1 h/d; 5 d/wk), sham exercise (sham), and non-treated controls (n = 8 per group). After 6 weeks of treatment, an intraperitoneal glucose tolerance test was performed and animals were euthanized for tissue analysis. By 5 weeks of treatment, controls had elevated fed and fasted glycemia (>11.1 and 7.1 mmol/L, respectively; both P < .05), whereas exercise and sham rats remained euglycemic. At euthanasia, there were elevations in fed insulin levels in exercise and sham rats compared with basal animals (both P < .05). Despite improvements in fed and fasting glucose levels in sham rats, glucose tolerance in sham-treated rats (intraperitoneal glucose tolerance test) was similar to controls, whereas glucose levels were similar in exercised trained and basal rats. After 6 weeks, gastrocnemius glycogen content was higher in exercised rats and sham rats when compared with age-matched controls, whereas muscle glucose transporter 4 levels were similar between groups. Compared with controls, the exercise group had increased beta cell proliferation, beta cell mass, and partial maintenance of normal islet morphology. Sham rats also displayed beta cell compensation, as evidenced by increased fasting insulin levels and partial preservation of normal islet morphology. Finally, at the time of euthanasia, plasma corticosterone was increased in sham and control rats but was at basal levels in the exercise group. In summary, both exercise and sham treatment delay the progression of type 2 diabetes mellitus in the male ZDF rat by distinct mechanisms related to pancreatic function and improvements in peripheral glucose disposal.