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Endocrinology Vol. 140, No. 10 4595-4600
Copyright © 1999 by The Endocrine Society


ARTICLES

Biotin Regulation of Pancreatic Glucokinase and Insulin in Primary Cultured Rat Islets and in Biotin- Deficient Rats1

Guillermo Romero-Navarro, Gabriela Cabrera-Valladares, Michael S. German, Franz M. Matschinsky, Antonio Velazquez, Juehu Wang and Cristina Fernandez-Mejia

From the Nutritional Genetics Unit (G.R.N., G.C.V., A.V., C.F.M.) Biomedical Research Institute, National University of Mexico; Hormone Research Institute (M.S.G., J.W.) University of California San Francisco; and Diabetes Research Center (F.M.M.) University of Pennsylvania, Medical Center

Address all correspondence and requests for reprints to: Cristina Fernandez-Mejia, Unidad de Genetica de la Nutricion, Instituto de Investigaciones Biomedicas Universidad Nacional Autonoma de Mexico (UNAM)/Instituto Nacional de Pediatria (INP), Av. del Iman 1, 4th floor, Mexico City, C.P. 04530, Mexico. E-mail: crisfern{at}servidor.unam.mx

Biotin has been reported to affect glucose homeostasis; however, its role on pancreatic islets of Langerhans has not been assessed. In this report, we demonstrate that physiologic concentrations of biotin stimulate glucokinase activity in rat islets in culture. Using the branched DNA (bDNA) assay, a sensitive signal amplification technique, we detected relative increases in 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 biotin on insulin release. Treatment with [10-6 M] biotin for 24 h increased insulin secretion. We extended our studies by analyzing the effect of biotin deficiency on pancreatic islet glucokinase expression and activity, as well 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 deficient rat. These data show that biotin affects pancreatic islet glucokinase activity and expression and insulin secretion in cultured islets.




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