title: The changes in adenine nucleotides measured in glucose-stimulated rodent islets occur in beta cells but not in alpha cells and are also observed in human islets.
abstract: Glucose metabolism by pancreatic beta and alpha cells is essential for stimulation of insulin secretion and inhibition of glucagon secretion. Studies using rodent islets have suggested that the ATP/ADP ratio serves as second messenger in beta cells. This study compared the effects of glucose on glucose oxidation ([U-14C]glucose) and adenine nucleotides (luminometric method) in purified rat alpha and beta cells. The rate of glucose oxidation at 1 mM glucose was higher in beta than alpha cells (4.5-fold, i.e. approximately 2-fold after normalization for cell size). It was more strongly stimulated by 10 mM glucose in beta cells (9-fold) than in alpha cells (5-fold). At 1 mM glucose, ATP levels were similar in both cell types, which corresponds to an approximately 2-fold higher concentration in alpha cells ( approximately 6.5 mM) than in beta cells ( approximately 3 mM). In beta cells, glucose dose-dependently increased ATP and decreased ADP levels, causing a rise in the ATP/ADP ratio from 2.4 to 11.6 at 1 and 10 mM, respectively. In alpha cells, glucose did not affect ATP and ADP levels, and the ATP/ADP ratio remained stable around 7.5. In human islets, the ATP/ADP ratio progressively increased between 1 and 10 mM glucose. In duct cells, which often contaminate human islet preparations, an increase in the ATP/ADP ratio sometimes occurred between 1 and 3 mM glucose. In conclusion, the present observations establish that the regulation of glucagon secretion by glucose does not involve changes in alpha cell adenine nucleotides and further support the role of the ATP/ADP ratio in the control of insulin secretion.
authors.affiliation: Unit of Endocrinology and Metabolism, Université Catholique de Louvain, B 1200 Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Detimary
authors.forename: S
authors.initials: S
authors.lastname: Dejonghe
authors.forename: Z
authors.initials: Z
authors.lastname: Ling
authors.forename: D
authors.initials: D
authors.lastname: Pipeleers
authors.forename: F
authors.initials: F
authors.lastname: Schuit
authors.forename: J C
authors.initials: JC
authors.lastname: Henquin
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology / Q000502:physiology*; D006019:Glycolysis; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose