Voluntary exercise under a food restriction condition decreases blood branched-chain amino acid levels, in addition to improvement of glucose and lipid metabolism, in db mice, animal model of type 2 diabetes

Abstract

Objectives Exercise is effective for preventing the onset and development of type 2 diabetes mellitus (T2DM) in human cases; however, the effect of exercise on the pathophysiology using animal models of T2DM has not been fully evaluated. Methods We applied voluntary exercise under pair-fed (P) conditions in db mice, an animal model of T2DM. Exercising (Ex) and sedentary (Se) mice were placed in a cage, equipped with a free or locked running wheel, for 4 weeks, respectively. The amount of food consumed by ad libitum-fed wild-type mice under the Se condition (ad-WT) was supplied to all mice, except ad libitum db mice (ad-db). Blood parameters and expression of the genes involved in nutrient metabolism were analyzed. Results PEx-db (pair-fed and exercising) mice showed significantly lower HbA1c, body weight and liver weight than PSe-db and ad-db mice. Decreased hepatic triglycerides in PEx-db mice corresponded to a lower expression of lipogenic enzyme genes in the liver. Moreover, PEx-db mice showed significantly lower plasma branched-chain amino acids (BCAA), arginine, proline, and tyrosine, in addition to increased skeletal muscle (SM) weight, than PSe-db and ad-db mice, in spite of little influence on the expression of the BCAA transaminase gene, in SM and WAT. Conclusion We found that exercise under a food restriction condition decreases several amino acids, including BCAA, and may improve insulin sensitivity more than mere food restriction. We propose that the decreased concentration of blood amino acids may be a valuable marker evaluating the effects of exercise on diabetic conditions.

Exercise Ameliorates Insulin Resistance of Type 2 Diabetes through Motivating Short-Chain Fatty Acid-Mediated Skeletal Muscle Cell Autophagy

“…Additionally, the long-term benefits of exercise therapy for T2DM have been recognized [10]. Exercise facilitates the decline of blood branched-chain amino acid [11], thereby promoting glucose and lipid metabolism in patients with T2DM [12]. Exercise also increases insulin sensitivity and reduces IR in T2DM by mediating the competing endogenous RNAs (CeRNAs) axis [13,14].…”

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

“…Using the same model of obesity, Cui et al22 reported that CR and treadmill running improved common cardiovascular risk factors, decreased plasma leptin, increased plasma adiponectin, and activated autophagy-related pathways in the cardiac muscle. Decreasing the caloric intake and increasing the energy expenditure by voluntary exercise in the hypoleptinemic ob/ob mouse reduced fasting hyperglycemia and hyperglucagonemia but failed to reduce plasma insulin levels 23,24. In the db/db mouse, a model characterized by insulin resistance, hyperglycemia, and hyperleptinemia as a result of a mutation that inactivates the leptin receptor, combining exercise and dietary energy restriction improved fasting blood glucose 25.…”

In Vivo Monitoring of Amino Acid Biomarkers from Inguinal Adipose Tissue Using Online Microdialysis-Capillary Electrophoresis

“…Isoleucine concentrations ranged from 74 to 219 μM, depending on experimental conditions. Leucine concentrations ranged from 109 to 349 μM and valine concentrations spanned 213 to 508 μM . These concentrations are significantly higher than the LODs for our MD-CE assay, suggesting that detection of the BCAAs in adipose tissue using this assay will not be an issue.…”