Enhanced Glucose Clearance in the Red Muscles of High Altitude Native Rats is Mediated by Activation of AMPK/AS160/GLUT-4 Translocation Signaling Pathway
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- Category: Vol. 85, September 2017
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Enhanced Glucose Clearance in the Red Muscles of High Altitude Native Rats is Mediated by Activation of AMPK/AS160/GLUT-4 Translocation Signaling Pathway, GHADA A. ABD ELALEEM and EMAN F. KHALEEL
Abstract
Background: Besides insulin, AMP-Activated Protein Kinase (AMPK) was shown to facilitate muscular glucose uptake in mammals.
Aim: To investigate the role of insulin and AMPK signaling pathways in glucose uptake in the red muscle of High Altitude (HA) native rats.
Methods: Male rats (n=8) with the same age, genetic background, diet and native to the natural area of Low Altitude (LA) and HA with or without Compound C (CC) treatment, an inhibitor of AMPK, were used. Later, fasting plasma glucose and insulin levels, i.p. glucose (IPGGT) and insulin tolerance tests (IPITT) were carried out. Glycogen levels, protein levels of the mediators involved in insulin and AMPK signaling and levels of microsomal and membranous levels of GLUT-4 were measured in the gastrocnemius muscle. Also, markers of oxidative stress and hormonal analysis were determined.
Results: HA rats had stable basal insulin levels and lower basal glucose levels and HOMA-IR with an overall enhance-ment in glucose clearance and insulin tolerance. Under basal conditions, Gastrocnemius muscles of HA rats had higher levels of membranous GLUT-4 with no alteration in the levels of p-IRS (tyr632), p-Akt and its downstream targets including p-mTOR, p-tuberin, and p70S6 kinase/IRS (ser307). However, HA rats showed significant increases in the levels of CPT-1, p-AMPK and its downstream target, p-AS 160. Also, HA rats had higher levels of lipid peroxidation (MDA and 4-HNE) and had higher circulatory leptin levels, all of which were significantly and positively correlated with levels of p-AMPK.
Conclusion: Our novel data is the first to show that activation of pAMPK/AS 160/GLUT-4 translocation is activated in the muscle of HA native rats, an effect that is responsible for reducing basal glucose levels and mediated by lipid peroxidation and leptin.