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Abstract
ObjectivesWe aimed at identifying genes related to hereditary type 2 diabetes expressed in the liver and the adipose tissue of spontaneous diabetic gerbils using suppression subtractive hybridization (SSH) screening.MethodsTwo gerbil littermates, one with high and the other with normal blood glucose level, from our previously bred spontaneous diabetic gerbil strain were used in this study. To identify differentially expressed genes in the liver and the adipose tissue, mRNA from these tissues was extracted and SSH libraries were constructed for screening. After sequencing and BLAST analyzing, up or down-regulated genes possibly involved in metabolism and diabetes were selected, and their expression levels in diabetic gerbils and normal controls were analyzed using quantitative RT-PCR and Western blotting.ResultsA total of 4 SSH libraries were prepared from the liver and the adipose tissue of gerbils. There are 95 up or down-regulated genes were identified to be involved in metabolism, oxidoreduction, RNA binding, cell proliferation, and differentiation or other function. Expression of 17 genes most possibly associated with diabetes was analyzed and seven genes (Sardh, Slc39a7, Pfn1, Arg1, Cth, Sod1 and P4hb) in the liver and one gene (Fabp4) in the adipose tissue were identified that were significantly differentially expressed between diabetic gerbils and control animals.ConclusionsWe identified eight genes associated with type 2 diabetes from the liver and the adipose tissue of gerbils via SSH screening. These findings provide further insights into the molecular mechanisms of diabetes and imply the value of our spontaneous diabetic gerbil strain as a diabetes model.
Highlights
Diabetes mellitus (DM) is a severe human disease and is the fourth cause of mortality
Expression of 17 genes most possibly associated with diabetes was analyzed and seven genes (Sardh, Slc39a7, Pfn1, Arg1, Cth, Sod1 and P4hb) in the liver and one gene (Fabp4) in the adipose tissue were identified that were significantly differentially expressed between diabetic gerbils and control animals
We identified eight genes associated with type 2 diabetes from the liver and the adipose tissue of gerbils via suppression subtractive hybridization (SSH) screening
Summary
Diabetes mellitus (DM) is a severe human disease and is the fourth cause of mortality. Genetic factors play major roles in the cause of type 2 diabetes [2]. In the high-fat diet (HFD) induced type 2 diabetes model, vital organs are not damaged; it is more suitable to explore the role of nutrition factors in diabetes. Modified animals, such as knock out of IRS-1, IRS-2, GLUT-4[3, 4], are limited to investigating pathogenic mechanisms because of dysfunction of one or two genes. Spontaneous diabetic models present hyperglycemia and insulin resistance and show more similar phenotypes and diabetes progression to human, are more suitable for studying genetic factors underlying diabetes. The possibility of using Mongolian gerbil as a diabetic model was first reported by Boquist who found that some gerbils in their colony had relatively higher fasting blood glucose and obesity [9]
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