Development and characterization of late-stage diabetes mellitus and -associated vascular complications

Abstract

Preclinical investigation is the key mark of medical research, as the major breakthroughs including treatment of devastating diseases in biomedical research have been led by animal studies. Type 2 diabetes mellitus (T2DM) is a predominant metabolic disorder having high prevalence of morbidity worldwide which create an urgent need to understand the pathogenesis, complication and other possible influences by development of appropriate animal model. High-fat diet (HFD) fed animals (21 days) were treated with single cycle of repetitive dose (SCRD) of streptozotocin (STZ; 40, 30 and 20 mg/kg/per day in three respective group at 1st, 3rd, and 5th day) and double cycle of repetitive dose (DCRD) of streptozocin (STZ) (20, 10 and 5 mg/kg/per day in three respective group at 1st, 3rd, and 5th day in one cycle and 21st, 23rd, 25th day in second cycle of treatment) to induce late-stage diabetic complications. Induction of hyperglycemia was assessed by fasting and postprandial blood glucose, HbA1c, insulin, C-peptide, pancreatic β-cells and dyslipidaemia up to 12 weeks. Combined treatment of HFD and STZ (20 mg/kg) in the DCRD manner were significantly induced late-stage diabetic complication with sustained hyperglycaemia, no mortality, increased HbA1c and dyslipidaemia, reduced insulin, C-peptide and beta cells. Moreover, biochemical and histological assessment of micro and macrovascular tissues confirmed the significant cardio-renal injury, endothelial and hepatic damage. The study confirmed the development of chronic diabetic model in rat mimicked to clinical pathology with associated micro and macrovascular abnormalities which can further explore the molecular aspects of diseases.