title: Differential Expression of Metabolism-related Genes in Liver of Diabetic Obese Rats.
abstract: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.
authors.affiliation: Department of Pharmacology, Dong-A University College of Medicine, Medical Science Research Center, Busan 602-714, Korea.
authors.forename: Eunhui
authors.initials: E
authors.lastname: Seo
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Park
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Park
authors.forename: Duk Kyu
authors.initials: DK
authors.lastname: Kim
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sook-Hee
authors.initials: SH
authors.lastname: Hong
references.citation: MMWR Morb Mortal Wkly Rep. 2004 Nov 19;53(45):1066-8
references.pmid: 15549021
references.citation: Prog Lipid Res. 2004 Mar;43(2):91-104
references.pmid: 14654089
references.citation: Diabetes Obes Metab. 1999 Sep;1(5):257-63
references.pmid: 11225637
references.citation: Curr Opin Lipidol. 2003 Jun;14(3):255-61
references.pmid: 12840656
references.citation: Diabetes. 1992 Nov;41(11):1422-8
references.pmid: 1397718
references.citation: Diabetes Care. 2001 Aug;24(8):1460-7
references.pmid: 11473087
references.citation: Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E654-62
references.pmid: 15562253
references.citation: Diabet Med. 1998 Jul;15(7):539-53
references.pmid: 9686693
references.citation: Diabetes. 2005 Dec;54 Suppl 2:S40-5
references.pmid: 16306339
references.citation: Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R21-31
references.pmid: 14734629
references.citation: Diabetes Res Clin Pract. 1994 Oct;24 Suppl:S317-20
references.pmid: 7859627
references.citation: Trends Endocrinol Metab. 2007 Mar;18(2):52-7
references.pmid: 17208448
references.citation: Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1750-4
references.pmid: 15284087
references.citation: Am J Physiol. 1982 Jul;243(1):E15-30
references.pmid: 7046470
references.citation: Diabetes. 1988 Dec;37(12):1595-607
references.pmid: 3056758
references.citation: BMJ. 2002 Aug 3;325(7358):232-3
references.pmid: 12153906