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.