Abstract
OBJECTIVE - Incidence of type II diabetes mellitus is rapidly increasing worldwide. This study aimed to investigate whether cyanidin-3-O-β-glucoside (C3G), or peptides with angiotensin converting enzyme (ACE) inhibitory activity, alone or in combination, alter glucose regulation in human primary myotubes derived from obese and obese diabetic individuals.
RESEARCH DESIGN AND METHODS - In cells treated with 10 μM, 100 μM of C3G, 150 μg/mL, 1500 μg/mL of peptide and their combinations, [3H]-2-deoxyglucose uptake and mRNA expression of multiple genes related to insulin resistance and glucose metabolism were determined by ’real-time’ PCR. Statistical analyses were performed using GraphPad Prism 7 (GraphPad Software, Inc, La Jolla, CA, USA). P < 0.05 was considered significant.
RESULTS - In the obese group, both low and high concentration of peptides with ACE inhibitory activity and the combination of these peptides with high C3G concentration significantly enhanced glucose uptake in the presence or absence of insulin. However, only high peptide concentration increased glucose uptake in the absence of insulin in the diabetic group. In the obese group, high concentration of peptide alone and its combination with low C3G down-regulated the mRNA expression of angiotensin II receptor, type 1 (AGTR-1) and FOXO1, and up-regulated the mRNA expression of insulin receptor substrate 1 (IRS-1), GLUT1 and GLUT4. Furthermore, the expression of AGTR-1 and FOXO1 were decreased with high peptide and its combinations of C3G in the diabetic group. Only high peptide concentration increased IRS-1 mRNA expression in the diabetic group.
CONCLUSIONS - C3G and peptides with ACE inhibitory activity improve glucose uptake potentially via the regulation of AGTR-1 and insulin-dependent signalling pathway (with insulin-like properties) in human primary myotubes. This provides a potential novel approach for the regulation of glucose metabolism in obese and diabetic individuals.