Immunohistochemical Evidence for the Presence of Glucokinase in the Gonadotropes and Thyrotropes of the Anterior Pituitary Gland of Rat and Monkey

Abstract

A recent report provides new evidence for the presence of glucokinase (GK) in the anterior pituitary. In the present study, immunohistochemistry was used to identify the cells containing GK in the pituitary of rats and monkeys. In rats, GK was detected as a generalized cytoplasmic staining in a discrete population of cells in the anterior pituitary. In colocalization experiments, the majority of cells expressing follicle-stimulating hormone (FSH) or luteinizing hormone (LH) also contained GK. In addition to the gonadotropes, GK was observed in a subpopulation of corticotropes and thyrotropes. GK was not detected in cells expressing growth hormone or prolactin. In monkeys, GK was also observed in a discrete population of cells. Intracellular distribution differed from the rat in that GK in most cells was concentrated in a perinuclear location that appeared to be associated with the Golgi apparatus. However, similar to rats, colocalization experiments showed that the majority of cells expressing FSH or LH also contained GK. In addition to the gonadotropes, GK was observed in a subpopulation of corticotropes and thyrotropes. In the monkey, only a few cells had generalized cytoplasmic staining for GK. These experiments provide further evidence for the presence of GK in the anterior pituitary. Although some corticotropes and thyrotropes contained GK, the predominant cell type expressing GK was gonadotropes. In view of the generally accepted role of GK as a glucose sensor in a variety of cells including the insulin-producing pancreatic β-cells as the prototypical example, it is hypothesized that hormone synthesis and/or release in pituitary cells containing GK may be directly influenced by blood glucose.

Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics

“…This result offers a plausible explanation for the efficacy of piragliatin in a clinical trial (9, 51) and illustrates the potential of this new class of antidiabetic agents. Evidence is increasing that glucose stimulates replication of normal ␤-cells, allowing their adaptative hyperplasia in insulin resistance states, for example, in pregnancy and obesity (74,76). If this proliferative glucose action depends on glucose metabolism, as current knowledge implies, it is predictable from the present data that it might be curbed in the diabetic state and that GKAs may repair this refractoriness.…”

Research and Development of Glucokinase Activators for Diabetes Therapy: Theoretical and Practical Aspects

“…GK has been discovered in the glucagons-producing alpha-cells of the pancreas (Bedoya et al 1987;Reimann et al 2008), nuclei of the hypothalamus (Levin et al , 2008, the tractus solitarius and the raphe nuclei of the brain stem , and in the gonadotropes and thyrotropes of the pituitary gland (Hille et al 1995;Matschinsky 2008;Sorenson et al 2007;Zelent et al 2006). There is convincing evidence that the enzyme may exist in the GLP1-secreting L-cells of the intestine (Reimann et al 2004(Reimann et al , 2006(Reimann et al , 2008 but its biological significance has been disputed, even though not compellingly (Murphy et al 2008).…”

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia

“…Glucokinase is also thought to play a role in glucose sensing in the hypothalamus [Spyer et al, 2000], anterior pituitary cells [Sorenson et al, 2007;Zelent et al, 2006] and gut endocrine cells [Jetton et al, 1994]. Recent studies suggest, however, that glucokinase does not function as the main gut glucose sensor in K and L cells that secrete the incretin hormones glucagon-like peptide (GLP-1) and glucose-dependent insulinotrophic peptide (GIP), which both play a role in the regulation of glucosestimulated insulin release by pancreatic b-cells [Murphy et al, 2009].…”