A Glucose Sensor Role for Glucokinase in Anterior Pituitary Cells

A Glucose Sensor Role for Glucokinase in Anterior Pituitary Cells Dorothy Zelent 1 , Maria L. Golson 1 , Brigitte Koeberlein 1 , Roel Quintens 2 , Leentje van Lommel 2 , Carol Buettger 1 , Heather Weik-Collins 1 , Rebecca Taub 3 , Joseph Grimsby 3 , Frans Schuit 2 , Klaus H. Kaestner 1 and Franz M. Matschinsky 1 1 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 2 Katholieke University of Leuven, Leuven, Belgium 3 Division of Metabolic Diseases, Hoffmann La Roche, Nutley, New Jersey Address correspondence and reprint requests to Franz M. Matschinsky, University of Pennsylvania School of Medicine, BiochemistryBiophysics, 501 Stemmler Hall, 36th & Hamilton Walk, Philadelphia, PA 19104. E-mail: matsch{at}pobox.upenn.edu Abstract Enzymatic activity of glucokinase was demonstrated, quantitated, and characterized kinetically in rat and mouse pituitary extracts using a highly specific and sensitive spectrometric assay. A previously proposed hypothesis that the glucokinase gene might be expressed in the pituitary corticotrophic cells was therefore reexamined using mRNA in situ hybridization and immunohistochemical techniques. No evidence was found that corticotrophs are glucokinase positive, and the identity of glucokinase-expressing cells remains to be determined. The findings do, however, suggest a novel hypothesis that a critical subgroup of anterior pituitary cells might function as glucose sensor cells and that direct fuel regulation of such cells may modify the classical indirect neuroendocrine pathways that are known to control hormone secretion from anterior pituitary cells. GKA, glucokinase activator GST, glutathione S-transferase POMC, proopiomelanocortin Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted April 14, 2006. Received February 1, 2006. DIABETES