Possible Modulation of Brain Visfatin by Metformin in Type 2 Diabetes Mellitus; Role of Inflammation and Oxidative Stress, OMAIMA M. ABD EL-WAHED, OLA M. TORK, MAHA M. GAMAL EL-DIN, LAILA RASHED and MAHA ZICKRI
Abstract
Background: Nicotinamide phosphoribosyltransferase (NAMPT)/Visfatin; an adipokine that has drawn attention in the last decade, is expressed in many tissues, including the brain, where it is involved in the mammalian salvage pathway of Nicotinamide Adenine Dinucleotide (NA)) synthesis. Role of Visfatin in human physiology and pathophysiology of different diseases including neuodegenerative conditions is still unclear and controversial.
Aim: The present work aims to study the changes in expression of Visfatin/NAMPT in the brain of diabetic rats following Metformin therapy and its possible association with peripheral and neuro-inflammation and oxidative stress in the brain.
Methods: 36 adult male rats were divided into 4 groups; control (1), metformin control (2), diabetic (3), metformin treated (4) groups. Metformin (100mg/kg body weight once each morning using oral gavage) was given for animals of metfoпnіn treated group 3 weeks after confirmation of diabetes for 4 weeks. Blood samples were collected for estimation of serum fasting glucose, fasting insulin and serum tumor necrosis factor-a (TNF-cx). Brain specimens were prepared for evaluation of Malondialdehyde (МОЛ) level, gene expression of Visfatin in addition to histological examination and morphometric study for measurement of area of glial cells.
Results: Elevation of serum TNF-a, brain МОЛ and increased area of glial cells were observed in diabetic rats. These changes were associated with up-regulation of brain Visfatin. Metformin significantly reduced TNF-a, МОЛ and area of glial cells which was associated with down-regulation of brain Visfatin.
Conclusion: Metformin suppresses expression of brain Visfatin in diabetic rats possibly through its ant.i-inilanunatory