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: Amin Hasanvand, Hossein Amini-Khoei, Mohammad-Reza Hadian, Alireza Abdollahi, Seyed Mohammad Tavangar, Ahmad Reza Dehpour, Elika Semiei, Shahram Ejtemaei Mehr
• Journal: Inflammopharmacology (Inflammopharmacology) Vol. 24 Issue 5 Pg. 207-219 (Oct 2016) ISSN: 1568-5608 [Electronic] Switzerland
• PMID: 27506528 (Publication Type: Journal Article)

Chemical References

• Hypoglycemic Agents
• Inflammation Mediators
• Metformin
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Diabetes Mellitus, Experimental (blood, drug therapy, pathology)
• Diabetic Neuropathies (blood, drug therapy, pathology)
• Disease Models, Animal
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Inflammation Mediators (antagonists & inhibitors, blood)
• Male
• Metformin (pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Wistar
• Signal Transduction (drug effects, physiology)