Molecular mechanisms underlying diabetic microvascular complications

• Published in: Journal of Clinical and Scientific Research 2016-04, Vol.5 (2), p.112-123
• Main Authors: Bitla AR, Harini Devi N
• Format: Article
• Language: English
• Subjects: Diabetes mellitus; Endothelial dysfunction; Epigenetics; Microvascular; Hyperglycaemia
• ISSN: 2277-5706; 2277-8357
• DOI: 10.15380/2277-5706.JCSR.16.01.003

Vascular complications are a major cause of morbidity and mortality in patients with diabetes mellitus. Diabetic microvascular complications include diabetic retinopathy, neuropathy and nephropathy. Hyperglycaemia-induced activation of metabolic pathways, hyperglycaemia-induced growth factors, components of metabolic syndrome and hyperglycaemia-induced epigenetic changes act through a common platform i.e endothelial dysfunction. Hyperglycaemia, is the initiating cause of diabetic tissue damage. Under conditions of hyperglycaemia, four important pathways are activated which shuttle glucose and its intermediates through alternate pathways especially the polyol pathway forming sorbitol which exerts an osmotic effect; advanced glycation end products which modify biomolecules and alter their functions; protein kinase C activation causing altered signal transduction and hexosamine pathway which forms uridine diphosphate) N-acetyl glucosamine which glycosylates transcription factors and increases expression of procoagulant molecules. Hyperglycaemia is thought to activate these four pathways through increased generation of superoxide anions. Though hyperglycaemia is thought to be essential to cause clinically important microangiopathy, there are other factors which predispose an individual to these complications. Hyperglyca-emiainduced epigenetic changes i.e., changes in the deoxyribonucleic acid (DNA) molecule due to causes outside the DNA molecule are currently being probed for their role in development and progression of vascular complications. The ultimate purpose of understanding these mechanisms is to devise therapeutic measures which will target these mechanisms and will help in preventing the development as well as delaying the progression of diabetic vascular complications and improve the quality of life in these patients.