A Glucose Sensor Role for Glucokinase in Anterior Pituitary Cells

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. Diabetes

Nutritional regulation of glucokinase: a cross-species story

“…The deduced 'avian GK protein' presents no amino acid modification at the glucose or ATP binding sites (170) , at the allosteric activator site and hydrophobic surface for GKA (171) , at the GK regulator (GKR) binding site except N166(K) and L355(F) that participate in the binding of GKRP (172,173) . Looking for hyperglycaemic mutations (avian species have a high basal glucose level and they are relatively insensitive to glucose-induced insulin release), we find some mutations located on amino acids showing mutations associated with mild hyperglycaemias of maturity-onset diabetes of the young type 2 (MODY2) (174) but no difference on hyperglycaemic mutations as indicated by Zelent et al (16) . There is no mutation on amino acid-activating mutation sites (175) .…”

“…This was further supported by the fact that GK is encoded by a single gene, but controlled by two specific promoters: one hepatic and one pancreatic (12,13) . More recently, the GK network has been largely enriched as GK has been found in several other cellular types, including neurons (glucose excited and glucose inhibited), enteroendocrine cells (K and L) (14) , a-cells (15) and pituitary gonadotropes (16) . The presence of GK in rodent pancreatic tissue was discovered more than 20 years ago (17) , and given that the activity of pancreatic GK is glucose dependent, this enzyme is today inseparable from the glucose sensor concept (18,19) .…”

A Fresh View of Glycolysis and Glucokinase Regulation: History and Current Status

“…The glycolytic pathway is characterized in some cell types (8 -10), in pancreatic beta cells (4,(11)(12)(13) and alpha cells (14), hepatocytes (15)(16)(17)(18)(19), certain specific pituitary cells (20), and brain neurons (21) by a specific feature. This is the expression of a fourth hexokinase isoenzyme, glucokinase, which has a K m value in the physiological range of blood glucose concentration (15)(16)(17)(22)(23)(24)(25).…”

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

“…Thus, pituitary leptin might serve as a glucostat, which would provide one mechanism by which it senses the nutritional state. Recent landmark studies [188,189] reported glucokinase expression in a subset of pituitary cells including thyrotropes and gonadotropes, which would allow them to monitor the changes in serum glucose. Our studies suggest that pituitary leptin may also be affected by this sensor.…”