Combination of metformin and berberine represses the apoptosis of sebocytes in high‐fat diet‐induced diabetic hamsters and an insulin‐treated human cell line

Obesity and insulin resistance affect metabolic reactions, but their ensuing contributions to macrophage metabolism remain insufficiently understood. We investigated the contributions of berberine and metformin combination to the inhibition of sebocyte apoptosis in high‐fat diet‐induced diabetic hamsters and an insulin‐treated human cell line. Golden hamsters were fed a high‐glucose high‐fat diet and administered a 6‐week treatment with a combination of metformin and two concentrations of berberine (100 or 50 mg·kg −1 ). Body weights of treated hamsters were remarkably reduced compared with those of controls. Histological examination indicated that berberine repressed liver fat accumulation. Moreover, insulin and glucose concentrations were noticeably decreased by the combination treatments. In glucose tolerance tests, hamsters receiving berberine displayed higher tolerance to glucose, compared with the control group. Sebocytes isolated from high‐fat diet‐induced diabetic hamsters and insulin‐treated human sebocytes displayed elevated cell death rates, which were attenuated by berberine and metformin treatments. Further studies showed that the effects of metformin and berberine on cellular apoptosis were mediated via the Bik pathway. Thus, berberine may effectively decrease circulating glucose levels, ameliorate insulin resistance, reduce body weight, and attenuate sebocyte apoptosis in diabetic hamsters, potentially decreasing vulnerability to the cardiovascular complications of diabetes. Significance of the study The present data indicate that insulin stimulates changes in the expression levels of cell death‐associated proteins, which participate in sebaceous gland diseases during obesity or diabetes. The anti‐apoptotic effects of BBR and MET in sebaceous gland cells are regulated partially by Bik expression. To the best of our knowledge, this study is the first to suggest cell death counteracting effects of BBR in hamster and human sebocytes as well as to propose BBR as an innovative therapeutic agent for insulin‐related sebaceous gland diseases, including acne.