engleski

Leptin and insulin receptor expression in the brain of diet induced diabetic, obese elderly rats/ treated with Liraglutide (Victoza) and Metformin

Introduction: Advancing age and obesity are the major risk factors for development of diabetes type 2. Occurrence of insulin resistance in brain is named ‘diabetes type 3’ and probably contributes to cognitive defect in Alzheimer. Anti-diabetic drugs, like Metformin and Liraglutide, may have different capacity to treat central insulin resistance. Method: Twenty week old male and female SD rats were divided in: control group and 3 groups fed high fat-high sugar diet (HSHFD). From fifty first week one HSHFD group was treated with Metformin (50 mg/kg/day s.c.) and another one with Liraglutide (0.3 mg/kg/day s.c). All groups were sacrificed at 65 weeks of age. Brain was fixed and immunostained for insulin (IR) and leptin (ObR) receptor. Results: Compared with control group, male rat groups on HSHFD had significantly higher expression of IR in hippocampus, while female group had decreased level of IR (P = 0.04). HSHFD generally reduced expression of ObR in hypothalamus. Both drugs, Metformin and Liraglutide increased hypothalamic ObR expression during HSHFD. Liraglutide had stronger effect in female group. Discussion – conclusion: It is well known that insulin resistance is related to obesity. Results indicate that there are gender differences in insulin signaling pathway. IR in brain supports cognitive functions, including learning and memory and it decreases in aging. Based on idea that reduced IR results with synapse loss it is possible that female group on HSHFD, more likely than male group, develop cognitive defect. Low levels of ObR in hypothalamus in male and female groups accompanies obesity. According to our results the HSHFD affects IR and ObR distribution in the brain. Also, Metformin and Liraglutide had sex specific capacity to treat central insulin resistance. Sources of Funding: This work has been supported in part by VIF-MEFOS-1 (Faculty of Medicine Osijek, Croatia) and by RECOOP HST grant. Ethical Approval: All experimental procedures are conformed to the European Guidelines for the Care and Use of Laboratory Animals (directive 86/609). They were approved by the by Hungarian Ethical Committee for Animal Research (IV/3796/2015). Acknowledgement: The study was supported by Cedars Sinai Medical Center’s International Research and Innovation in Medicine Program, the Association for Regional Cooperation in the Fields of Health, Science and Technology (RECOOP HST Association) and the participating Cedars – Sinai Medical Center - RECOOP Research Centers (CRRC).

obesity; diabetes; insuline resistance; leptin resistance; Liraglutide; Metformin

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