Korean J Physiol Pharmacol.  2010 Apr;14(2):99-103. 10.4196/kjpp.2010.14.2.99.

Differential Expression of Metabolism-related Genes in Liver of Diabetic Obese Rats

• Seo E
• Park EJ
• Park MK
• Kim DK
• Lee HJ
• Hong SH

• KMID: 1457675
• DOI: http://doi.org/10.4196/kjpp.2010.14.2.99

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.

Keyword

OLETF; LETO; Type 2 diabetes; Glucose metabolism; Lipid metabolism; Differential expression

MeSH Terms

Animals
Blood Glucose
Cholesterol
Diabetes Mellitus, Type 2
Gene Expression
Gluconeogenesis
Glucose
Glycolysis
Humans
Hyperinsulinism
Insulin
Insulin Resistance
Lipid Metabolism
Liver
Male
Obesity
Plasma
Rats
Rats, Inbred OLETF
RNA, Messenger
Triglycerides
Blood Glucose
Cholesterol
Glucose
Insulin
RNA, Messenger
Triglycerides

Figure

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  Fig. 1. Analysis of expression of glucose metabolism related genes in OLETF and LETO rats by quantitative real-time PCR. Values represent means±SEM of LETO rats (n=10), and OLETF rats (n=10). ∗p<0.05 vs. LETO rats.

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  Fig. 2. Analysis of lipid distribution. (A) Plasma TG and TC levels of OLETF and LETO rats. Plasma TG and TC levels were significantly higher in OLETF than LETO rats. (B) Hepatic TG and TC levels of OLETF and LETO rats. There were no significant differences in hepatic TG and TC levels between OLETF and LETO rats. (C) Hepatic histology of LETO and OLETF rats (H&E stain, ×40). Values represent means±SEM of LETO rats (n=10), and OLETF rats (n=10). ∗p<0.05 vs. LETO rats.

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  Fig. 3. Analysis of the expression of lipid metabolism related genes by quantitative real-time PCR. (A) mRNA levels of lipid synthesis related genes in OLETF and LETO rats. Expression of HMGCR and SCD1 genes were significantly higher in OLETF than in LETO rats. (B) mRNA levels of fatty acid oxidation and lipid transport related genes in OLETF and LETO rats. The expression of HL was significantly higher in OLETF than LETO rats. Values represent means±SEM of LETO rats (n=10), and OLETF rats (n=10). ∗p<0.05 vs. LETO rats.

Reference

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