The alpha-glucosidase inhibitor miglitol affects bile acid metabolism and ameliorates obesity and insulin resistance in diabetic mice

Objective. Alpha-glucosidase inhibitors (alpha-GIs) show various anti-diabetic or anti-obesity effects in addition to the suppression of postprandial hyperglycemia. Based on recent observations that bile acids (BAs) are involved in glucose and energy homeostasis, we examined the ability of miglitol, an alpha-GI, to influence BA metabolism and ameliorate insulin resistance and obesity. Materials/methods. NSY mice, representing an obese type 2 diabetic model, were fed with a high-fat diet and treated with miglitol for 4 or 12 weeks. BAs were quantified in feces, blood from the portal vein or the vena cava and in the liver. The gene expression of type 2 iodothyronine deiodinase (D2) in brown adipose tissues, gluconeogenetic enzymes in the liver and adipoldnes in epididymal fat was measured, and portal blood glucagon-like peptide-1 (GLP-1) levels, body weight changes, glucose tolerance along with insulin sensitivity were evaluated. Results. Miglitol significantly increased BAs in both feces and portal blood while the hepatic BA level was reduced. The drug clearly enhanced active GLP-1 secretion into the portal blood and there was a good positive correlation between the active GLP-1 levels and portal blood BA concentrations. D2 expression in brown adipose tended to increase in association with the elevated BA concentrations. Miglitol ameliorated body weight gain, glucose intolerance, insulin resistance and inflammatory adipokine upregulation that were induced by a high-fat diet. Conclusions. Collectively, miglitol substantially affects BA regulation in mice and this novel finding may explain in part the known favourable effects of the drug on diabetes and obesity. (C) 2013 Elsevier Inc. All rights reserved.