Peripheral iInsulin rResistance iInduced by sStreptozotocin and mModified Ddiets: iImplications for hHippocampal sStructural and fFunctional Iintegrity

摘要: Background: An inverse association has been established between indices of insulin resistance and hippocampal structural and functional integrity.Aim: We compared hippocampal-dependent function and morphology across rat models of insulin resistance induced by streptozotocin (STZ) with and without modified diets. Methods: Rats were randomized to receive either multiple low-dose STZ (30 mg/kg; 5 successive days) with or without post-feeding with high-fructose drink (HFrD) or high-fat diet (HFD). At 30 or 60 days of such feeding, spatial memory was assessed by the Morris water maze technique, after which the animals were sacrificed. Fasting plasma insulin and glucose were then assayed, followed by estimation of homeostatic model assessment of insulin resistance (HOMA-IR). Moreover, the perfused brains of the rats were studied histologically by the Congo red technique. Oral glucose tolerance test was performed 48 hours to killing the rats by challenging rats with oral glucose (2 g/kg) followed by estimation of blood glucose at 0, 30, 60 and 90 minutes interval. Results: The use of intraperitoneal STZ with or without modified diets triggered insulin resistance with variable degrees of biochemical, neurobehavioral and hippocampal structural perturbations that were most pronounced in the STZ-injected rats post-fed HFrD or HFD for 30 or 60 days; as opposed to those on STZ, HFD or HFrD alone.Conclusion: These findings have implications and relevance for future studies aimed at exploring the association between insulin resistance and hippocampal structural and functional integrity.