Development of an Experimental Animal Screening Model for Induction of type-3 Diabetes Mellitus using High-fat Diet, Streptozotocin, and Nicotinamide

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ABSTRACT Purpose: To develop a screening method for the induction of type-3 diabetes mellitus (T3DM) in experimental animals. Materials and Methods: Twelve Albino Wistar rats were divided into normal control (NC) and disease control (DC) group. Animals of NC were fed with high-fat diet (HFD) for four weeks followed by intraperitoneal administration of nicotinamide (230 mg/kg) and streptozotocin (STZ) (65 mg/kg). Body weight (BW) and blood glucose levels (BGL) were measured from week 1 to 4. Glycosylated hemoglobin (HbA1C) levels were estimated on week 4. Behavioral parameters including Morris water maze test (MWMT), T-maze test, and rota-rod test were recorded. Estimation of acetylcholine (ACh) and acetylcholinesterase (AChE) was conducted on week 4. Histopathological analysis of brain hippocampus was undertaken in three animals of each group. Results: DC group showed significant elevation in levels of BW and BGL with P value < 0.05. Levels of HbA1C increased significantly in DC group with P value < 0.0001. DC group showed a significant increase (P value < 0.05 [week 1] and P value < 0.001 [weeks 2–4]) in escape latency and elapsed time in MWMT and T-maze test, respectively. In DC group, elapsed time decreased significantly (P value < 0.05 [week 1] and P value < 0.001 [weeks 2–4]) in rota-rod test. A significant deviation in the levels of ACh and AChE was recorded with P value < 0.0001. Histopathology of hippocampus part of DC group showed notable increase in the number of β-amyloid plaque. Conclusion: Animals administered with HFD, nicotinamide, and STZ showed dementia along with the diabetic condition suggesting the induction of T3DM.