Reduced glucose-6-phosphorylase and NADPH generating enzyme activities associated with glibenclamide induced hypoglycemia and hypoinsulinemia in genetically obese mice.
Addition of phenobarbital, an inducer of the liver mixed function oxidase system, to sulphonylurea regimen improves insulin sensitivity and intracellular glucose handling in patients with non-insulin dependent diabetes mellitus. The inducer also activates liver NADPH synthesis and its availability for mono-oxygenase reactions. In this study we further evaluated the mutual relationship between glucose and drug metabolism and the effect of sulphonylurea therapy by using genetically obese female mice. The mice were treated with glibenclamide, phenobarbital or both. Glibenclamide reduced blood glucose and plasma insulin levels indicating improved insulin sensitivity in the mice. Total glucose phosphorylating, delivering and NADPH generating enzyme activities were reduced together with decreased microsomal protein content and the amount of smooth endoplasmic reticulum in the liver. Phenobarbital had an opposite effect: the drug induced liver drug metabolism and increased hepatic glucose phosphorylating and NADPH generating enzyme activities. Treatment with glibenclamide seems to reduce serum immunoreactive insulin levels, microsomal enzyme function and NADPH generating enzyme activities in genetically obese mice.
Karvonen
I
I
Department of Internal Medicine and Pathology, University of Oulu, Finland.
Sormunen
R
R
Huupponen
R
R
Sotaniemi
E A
EA
D000818:Animals; D017920:Antiporters; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology*; D007003:Hypoglycemia / Q000139:chemically induced*; D007328:Insulin / Q000097:blood*; D008099:Liver / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008861:Microsomes / Q000737:chemistry; D009004:Monosaccharide Transport Proteins; D009249:NADP / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010770:Phosphotransferases / Q000378:metabolism; D011506:Proteins / Q000032:analysis
D017920:Antiporters; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011506:Proteins; C503532:Slc37a4 protein, mouse; C111261:glucose 6-phosphate(transporter); D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D010770:Phosphotransferases; D005905:Glyburide; D010634:Phenobarbital