Exercise-induced alterations in pancreatic oxidative stress and mitochondrial function in type 2 diabetic Goto-Kakizaki rats

Haider Raza, Annie John, Jasmin Shafarin, Frank C. Howarth

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Progressive metabolic complications accompanied by oxidative stress are the hallmarks of type 2 diabetes. The precise molecular mechanisms of the disease complications, however, remain elusive. Exercise-induced nontherapeutic management of type 2 diabetes is the first line of choice to control hyperglycemia and diabetes associated complications. In this study, using 11-month-old type 2 Goto-Kakizaki (GK) rats, we have investigated the effects of exercise on mitochondrial metabolic and oxidative stress in the pancreas. Our results showed an increase in the NADPH oxidase enzyme activity and reactive oxygen species (ROS) production in GK rats, which was inhibited after exercise. Increased lipid peroxidation and protein carbonylation and SOD activity were also inhibited after exercise. Interestingly, glutathione (GSH) level was markedly high in the pancreas of GK diabetic rats even after exercise. However, GSH-peroxidase and GSH-reductase activities were significantly reduced. Exercise also induced energy metabolism as observed by increased hexokinase and glutamate dehydrogenase activities. A significant decrease in the activities of mitochondrial Complexes II/III and IV were observed in the GK rats. Exercise improved only Complex IV activity suggesting increased utilization of oxygen. We also observed increased activities of cytochrome P450s in the pancreas of GK rats which was reduced significantly after exercise. SDS-PAGE results have shown a decreased expression of NF-κB, Glut-2, and PPAR-Υ(hooked) in GK rats which was markedly increased after exercise. These results suggest differential oxidative stress and antioxidant defense responses after exercise. Our results also suggest improved mitochondrial function and energy utilization in the pancreas of exercising GK rats.

Original languageEnglish
Article numbere12751
JournalPhysiological Reports
Volume4
Issue number8
DOIs
Publication statusPublished - Apr 1 2016

Keywords

  • Energy metabolism
  • Exercise
  • GK rats
  • Mitochondria
  • Oxidative stress
  • Pancreas
  • Type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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