title: Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy.
abstract: Diabetic neuropathy (DN) is characterized as Hyperglycemia activates thdisturbed nerve conduction and progressive chronic pain. Inflammatory mediators, particularly cytokines, have a determinant role in the pathogenesis of neuropathic pain. The activity of adenosine monophosphate protein kinase (AMPK), an energy charge sensor with neuroprotective properties, is decreased in diabetes. It has been reported that activation of AMPK reduces the systemic inflammation through inhibition of cytokines. In this study, we aimed to investigate the probable protective effects of AMPK on DN in a rat of diabetes. DN was induced by injection of streptozotocin (65 mg/kg, i.p.). Motor nerve conduction velocities (MNCV) of the sciatic nerve, as an electrophysiological marker for peripheral nerve damage, were measured. Plasma levels of IL-6, TNF-α, CRP were assessed as relevant markers for inflammatory response. Also, the expression of phosphorylated AMPK (p-AMPK) and non-phosphorylated (non-p-AMPK) was evaluated by western blotting in the dorsal root ganglia. Histopathological assessment was performed to determine the extent of nerve damage in sciatic nerve. Our findings showed that activation of AMPK by metformin (300 mg/kg) significantly increased the MNCV and reduced the levels of inflammatory cytokines. In addition, we showed that administration of metformin increased the expression of p-AMPK as well as decline in the level of non p-AMPK. Our results demonstrated that co-administration of dorsomorphin with metformin reversed the beneficial effects of metformin. In conclusion, the results of this study demonstrated that the activation of AMPK signaling pathway in diabetic neuropathy might be associated with the anti-inflammatory response.
authors: Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Amin
authors: A
authors: Hasanvand
authors: Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.|Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Hossein
authors: H
authors: Amini-Khoei
authors: Department of Physical Therapy, Rehabilitation Faculty, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mohammad-Reza
authors: MR
authors: Hadian
authors: Department of Pathology, Imam Khomini Complex Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Alireza
authors: A
authors: Abdollahi
authors: Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Seyed Mohammad
authors: SM
authors: Tavangar
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Ahmad Reza
authors: AR
authors: Dehpour
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Elika
authors: E
authors: Semiei
authors: Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran. ejtemam@gmail.com.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. ejtemam@gmail.com.
authors: Shahram Ejtemaei
authors: SE
authors: Mehr
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D003929:Diabetic Neuropathies / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D008687:Metformin; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Cytokines; Diabetic neuropathy; Inflammatory response; MNCV; Rat