Cardiac Muscle Protein Catabolism in db / db Obese Mice , a Type II Diabetes Mellitus Model

Muscle wasting (skeletal and cardiac) is associated with increasing morbidity and mortality. Muscle wasting is primarily the result of increased proteolysis within muscle that leads to excessive degradation of structural proteins such as actin. Accelerated muscle protein degradation is associated with insulin resistance. Muscle protein metabolism in cardiac muscle under conditions of insulin resistance has been understudied. In the current study, we measured protein degradation in cardiac muscle of db/db obese mice. Insulin resistance increased degradation of both soluble and the myofibrillar protein. Insulin/IGF-1 signaling pathways regulate cardiac muscle proteolysis. In the heart muscles from db/db mice, we found that Insulin Receptor Substrate-1 (IRS-1) tyrosine phosphorylation and Akt phosphorylation were decreased causing decreased insulin signaling, and transcription factors FoxO 1 and 3 are dephosphorylated (activated) leading to increased protein degradation. Expression of E3 ubiquitin mRNAs and chymotrypsin-like activity of the proteasome were increased, indicating that the ubiquitin-proteasome system was activated in obese mouse heart. Cardiac muscle protein catabolism was associated with increased serum free fatty acid and inflammatory cytokines in heart, as well as decreased plasma levels of adiponectin. In our previous study, we showed that a decrease in adiponectin and increase in free fatty acid could cause insulin resistance and muscle proteolysis. In this study, we conclude that insulin resistance (resulting from reduced IRS-1/Akt signaling), associated with activation of the ubiquitin-proteasome proteolytic pathway, results in accelerated proteolysis in obese cardiac muscle. Min Li1,2, Faten Hassounah2 and Xiaonan H Wang2* 1Guanganmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China 2Renal Division, Department of Medicine, Emory University, Atlanta, GA, USA Cardiac Muscle Protein Catabolism in db/db Obese Mice, a Type II Diabetes Mellitus Model Citation: Li M, Hassounah F, Wang XH (2015) Cardiac Muscle Protein Catabolism in db/db Obese Mice, a Type II Diabetes Mellitus Model. J Diabetes Metab Syndr Disord 2: 004.