title: Long term in vitro effects of streptozotocin, interleukin-1, and high glucose concentration on the activity of mitochondrial dehydrogenases and the secretion of insulin in pancreatic islets.
abstract: When cultured mouse pancreatic islets were exposed for 30 min to streptozotocin (STZ; 1.8 mM) and then maintained for 7 days in tissue culture, they displayed a decreased secretory response to D-glucose and an impairment of both FAD-linked glycerophosphate dehydrogenase and NAD-dependent 2-ketoglutarate dehydrogenase specific activities, with little change in either NAD-linked glycerophosphate dehydrogenase or glutamate dehydrogenase activity. The enzymatic defect was not reproduced by prolonged exposure of either rat islets to interleukin-1 (10 U/ml) or mouse islets to a high concentration of D-glucose (28 mM). In the former, but not latter, situation, the secretory response to D-glucose was again impaired. These findings reveal that STZ, but not all beta-cytotoxic agents, lowers the activity of selected islet mitochondrial dehydrogenases. Such enzymatic defects, especially the suppression of FAD-linked glycerophosphate dehydrogenase, may explain the preferential alteration of the B-cell metabolic and secretory responses to D-glucose, as previously observed in islets of adult rats injected with STZ during the neonatal period.
authors.affiliation: Laboratory of Experimental Medicine, Brussels Free University, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Rasschaert
authors.forename: D L
authors.initials: DL
authors.lastname: Eizirik
authors.forename: W J
authors.initials: WJ
authors.lastname: Malaisse
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D007328:Insulin; D007375:Interleukin-1; D011506:Proteins; D011994:Recombinant Proteins; D009243:NAD; D005182:Flavin-Adenine Dinucleotide; D013311:Streptozocin; D004247:DNA; D005993:Glycerolphosphate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D005969:Glutamate Dehydrogenase; D005947:Glucose