Biotin regulation of pancreatic glucokinase and insulin in primary cultured rat islets and in biotin-deficient rats

Biotin has been reported to affect glucose homeostasis; however, its role o n pancreatic islets of Langerhans has not been assessed. In this report, we demonstrate that physiologic concentrations of biotin stimulate glucokinas e activity in rat islets in culture. Using the branched DNA (bDNA) assay, a sensitive signal amplification technique, we detected relative increases i n glucokinase mRNA levels of 41.5 +/- 13.% and 81.3 +/- 19% at 12 and 24 h respectively in islets treated with [10(-6) M] biotin. Because glucokinase activity controls insulin secretion, we also investigated the effect of bio tin on insulin release. Treatment with [10(-6) M] biotin for 24 h increased insulin secretion. We extended our studies by analyzing the effect of biot in deficiency on pancreatic islet glucokinase expression and activity, as w ell as insulin secretion. Our results show that islet glucokinase activity and mRNA are reduced by 50% in the biotin deficient rat. Insulin secretion in response to glucose was also impaired in islets isolated from the defici ent rat. These data show that biotin affects pancreatic islet glucokinase a ctivity and expression and insulin secretion in cultured islets.