Insulin and dietary fructose induce stearoyl-CoA desaturase 1 gene expression of diabetic mice.
The transcription and mRNA levels of murine liver stearoyl-CoA desaturase 1 (SCD1) are induced 11- and 45-fold, respectively, by feeding fasted normal mice with a fat-free, high carbohydrate diet (Ntambi, J. M. (1992) J. Biol. Chem. 267, 10925-10930). In this study, we used streptozotocin-induced diabetic mice to study the regulatory role of carbohydrate and insulin on expression of the SCD1 gene in liver. Fructose administration to fasted diabetic mice induced a 2-fold increase in SCD1 mRNA within 6 h and a 23-fold increase within 24 h. Similarly, insulin administration to diabetic mice induced SCD1 mRNA from 4-fold within 4 h to 22-fold within 24 h. Insulin plus fructose, however, achieved full induction, with a 45-fold increase of SCD1 mRNA and a 10-fold increase in SCD1 transcription within 24 h. Additionally, the effect of insulin on SCD1 mRNA was inhibited 75% with dibutyryl-cAMP and theophylline administration and 70% by cycloheximide administration. Synthesis of liver albumin mRNA showed little change upon dietary manipulation or insulin treatment. Our data demonstrate that insulin and dietary fructose or a metabolite of fructose positively regulate the expression of the SCD1 gene in mouse liver.
Department of Biochemistry, University of Wisconsin-Madison 53706.
K M
KM
Waters
J M
JM
Ntambi
D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D004040:Dietary Carbohydrates; D005632:Fructose / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D004040:Dietary Carbohydrates; D007328:Insulin; D012333:RNA, Messenger; D005632:Fructose; D003513:Cycloheximide; D000242:Cyclic AMP; D013230:Stearoyl-CoA Desaturase