Induction of Type 3 Diabetes mellitus by the Administration of Smaller Doses of Aluminium Chloride to the STZ Pretreated Rats

Abstract

The present study is designed to develop Type-3 diabetes mellitus characterized by insulin resistance, mainly at the brain level. The experimental rats in group-1: received vehicle (5 ml/kg, i.p.) for 28 days, group-2-4: received aluminium chloride (AlCl3) (12.5, 25, and 50 mg/kg, i.p.) daily for 28 days, group-5: received single dose of STZ (45 mg/kg, i.p.), and group-6-8: received STZ and AlCl3 (12.5, 25, and 50 mg/kg, i.p. daily for 28 days) from the third day of STZ administration. The behavioral analysis was initiated on the 29th day, estimating locomotor activity using an open field test, learning and memory-related functions using elevated plus maze (EPM) and morris water maze (MWM) tests. Afterwards, the rats were sacrificed, and brain and blood were collected for whole-brain neurochemical and plasma biochemical assays, including glucose, insulin, nitrite, MDA and amyloid-beta levels. The brain tissues were sectioned, followed by H&E and congo red staining for histopathological examination. The results obtained demonstrated that the STZ pretreatment and AlCl3 (12.5 mg/kg) treatment significantly impaired the cognition in EPM and MWM. Also, the STZ pretreatment and AlCl3 (12.5 mg/kg) treatment significantly increased the brain glucose levels, brain insulin levels, lipid peroxidation and amyloid levels, suggesting the development of hyperinsulinemia, insulin resistance and amyloid pathology. Further, STZ pretreatment and AlCl3 (12.5 mg/kg) treated rats produced the marked degenerated neurons, neuronal loss, and the marked deposition of amyloid fibrils suggesting the development of neurodegenerative changes. In conclusion, the present findings suggested that administering low doses of AlCl3 to the STZ pretreated experimental rats results in the development of marked hyperinsulinemia, insulin resistance, cognitive impairment, amyloid-beta deposition, and neuronal degeneration, reflects the features of Type-3 diabetes mellitus (T3DM).