1622-P: Complex Mechanisms Underlie the Antidiabetic Effect of Tempol in Experimentally Induced Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is a vastly growing worldwide health problem which imposes public health, social, as well as economic burden. Multifactorial and complicated pathophysiological pathways may underlie DM. Attention has been given for the search of polymodal therapeutic molecules. Herein, we tested the capacity of tempol, a known superoxide dismutase-mimetic in the treatment of experimentally induced DM. Thirty male Wistar rats weighing 150-200 g were equally divided into: 1- Control group (rats received a single intra-peritoneal injection of citrate buffer for 4 weeks), 2- Untreated diabetic group, and 3- Tempol treated diabetic group. At the end of the study blood samples were collected for the measurement of fasting blood glucose, fasting blood insulin, liver function, kidney function, oxidative stress markers, and inflammatory markers. Pancreas, skeletal muscles, and liver were removed for histopathological, immunohistochemical and RT-PCR studies. Treatment with tempol significantly improved glycemic status, insulin secretion, sensitivity and reserve. Tempol preserved both liver and kidney functions. Tempol also significantly enhanced energy status, and countered structural changes, inflammation, and apoptosis of pancreatic tissue. Tempol significantly upregulated pancreatic AMPK, and skeletal muscle and hepatic glucose transporters. Interestingly, tempol demonstrated an endogenous stem cells recruitment capacity. In conclusion, tempol exhibited a potential capacity to counter the complexity of the underlying mechanisms in DM. Disclosure Y.Naguib: None.