Interleukin-1 beta inhibits glucokinase activity in clonal HIT-T15 beta-cells.
Interleukin-1 beta (IL-1 beta) has been implicated in the pathogenesis of insulin-dependent diabetes mellitus. In the present study we have investigated the effects of IL-1 beta on glucose metabolism in clonal HIT-T15 beta cells. In the short-term (1 h), 25 U/ml IL-1 beta significantly increased the rates of insulin release and glucose utilisation, but not glucose oxidation. In contrast, after 48 h, IL-1 beta inhibited insulin release and glucose utilisation and oxidation. By assaying enzymes (hexokinase, glucokinase, pyruvate dehydrogenase, glucose 6-phosphatase) and nucleotides (ATP, ADP) associated with the regulation of glycolysis and glucose oxidation, we conclude that the inhibitory effects of IL-1 beta may be due to impaired glucokinase activity.
Diabetes Section, Glaxo Research Laboratories, Research Triangle Park, NC.
M
M
Beggs
G
G
Beresford
J
J
Clarke
R
R
Mertz
J
J
Espinal
P
P
Hammonds
D000227:Adenine Nucleotides / Q000378:metabolism; D002999:Clone Cells / Q000187:drug effects / Q000201:enzymology; D005941:Glucokinase / Q000037:antagonists & inhibitors*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D000227:Adenine Nucleotides; D007328:Insulin; D007375:Interleukin-1; D011768:Pyruvate Dehydrogenase Complex; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose