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Differential hexosamine biosynthetic pathway gene expression with type 2 diabetes
Megan Coomer1, M Faadiel Essop1
1Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7600, South Africa.
Molecular Genetics and Metabolism Reports
|November 30, 2016
Summary
Diabetic individuals show altered expression of hexosamine biosynthetic pathway (HBP) genes, including lower OGA and OGT. Ethnic differences in GFPT2 expression were also observed, suggesting HBP gene regulation
Area of Science:
- Biochemistry and Molecular Biology
- Metabolic Pathways
- Genetics and Genomics
Background:
- The hexosamine biosynthetic pathway (HBP) is crucial for protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc).
- HBP flux is linked to glucose metabolism, insulin resistance, and type 2 diabetes.
- Key regulatory genes of HBP include OGT, OGA, GFPT1, and GFPT2.
Purpose of the Study:
- To investigate differential gene expression of HBP regulators in diabetic and pre-diabetic individuals.
- To explore potential ethnic variations in HBP gene expression profiles.
- To assess the diagnostic utility of HBP gene regulation in diabetes.
Main Methods:
- Recruitment of 60 volunteers (Mixed Ancestry and Caucasian) classified as control, pre-diabetic, or diabetic.
- RNA extraction from leukocytes and quantitative real-time PCR to determine OGT, OGA, GFPT1, and GFPT2 expression levels.
- Statistical analysis to compare gene expression between groups and ethnicities.
Main Results:
- Diabetic individuals exhibited significantly lower OGA expression compared to controls.
- Pre-diabetic and diabetic subjects showed reduced OGT expression.
- GFPT2 expression was decreased in pre-diabetic and diabetic Caucasians, with notable ethnic differences observed in GFPT2 expression between Mixed Ancestry and Caucasian individuals.
Conclusions:
- Differential gene expression of HBP regulators is evident between diabetic and non-diabetic individuals.
- Distinct ethnic-specific gene expression profiles within the HBP pathway exist.
- Aberrant HBP gene regulation may serve as a diagnostic marker and identify susceptibility genes across different ethnic groups.
Keywords:
Fasting blood glucoseGFPT, glutamine:fructose-6-phosphate amidotransferaseGene expressionHBP, hexosamine biosynthetic pathwayHexosamine biosynthetic pathwayLeukocytesO-GlcNAc, O-linked β-N-acetylglucosamineOGA, β-N-acetylglucosaminidaseOGT, O-linked β-N-acetylglucosaminyl transferasePre- and overt diabetes
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