01 March 2018 : Laboratory Research
Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling PathwayCaijuan Wang1ADE, Yujiao Deng1BC, Yenan Yue1BDF, Wenting Chen1BCF, Yu Zhang1BF, Guifang Shi1CF, Zhongming Wu1ADG*
Med Sci Monit 2018; 24: LBR1241-1250
BACKGROUND: Diabetes mellitus (DM) is characterized by a decreased blood level of glutamine (Gln), which may contribute to the disturbance in the effect of insulin on skeletal muscle. Therefore, it is crucial to study how to improve the effect of insulin on skeletal muscle by increasing Gln. In the present study, we investigated the effect of Gln on the hypoglycemic action of insulin in skeletal muscle L6 cells at high glucose levels through the insulin signaling pathway and glycogen synthesis pathway.
MATERIAL AND METHODS: The L6 cells were cultured in and stimulated by Gln and insulin. The glutamine analogue, L-Gamma-Glutamyl-p-nitroanilide (GPNA), was used for verifying the effect of Gln. The expression of insulin signaling molecules, including phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B (AKT), protein kinase C zeta (PKCz), and glucose transporter 4 (GLUT4), were detected by real-time PCR and Western blot analysis, GLUT4 translocation was observed by immunofluorescence staining, glycogen synthase kinase (GSK) was analyzed by Western blotting, and glucose uptake was measured by glucose oxidase method (GOD).
RESULTS: The results demonstrated that Gln combined with insulin remarkably up-regulated PI3K and PDK1 and also increased AKT and PKCz phosphorylation. The present study shows that Gln enhanced the impact of insulin on GLUT4 and its translocation. The results of glucose uptake and GSK phosphorylation further confirmed the hypoglycemic effect of Gln accompanied with insulin. The hypoglycemic effect of Gln was reversed by GPNA.
CONCLUSIONS: These findings suggest that Gln enhances the hypoglycemic role of insulin through the PI3K/AKT/GLUT4 signaling pathway and glycogen synthesis pathway.
Keywords: Glucose Metabolism Disorders, Glutamine, Insulin
12 September 2022 : EditorialEditorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)
Med Sci Monit 2022; 28:e938365
16 September 2022 : Review articleEffects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Rev...
Med Sci Monit In Press; DOI: 10.12659/MSM.938141
12 September 2022 : Clinical ResearchEffect of Vitamin D Concentration on Course of COVID-19
Med Sci Monit In Press; DOI: 10.12659/MSM.937741
29 August 2022 : Database AnalysisTranscriptome Analysis of Peripheral Blood Mononuclear Cells Response in Patients with Severe COVID-19 Reve...
Med Sci Monit 2022; 28:e937532
29 Sep 2022 : Animal ResearchEffect of Antilogous Platelet-Rich Plasma on the Revascularization of Rabbit Prefabricated Flap
Med Sci Monit In Press; DOI: 10.12659/MSM.937718
26 Sep 2022 : Clinical ResearchDistribution and Determinants of Plasma Homocysteine Levels in a Preconception Population: A Retrospective ...
Med Sci Monit In Press; DOI: 10.12659/MSM.937987
26 Sep 2022 : Clinical ResearchLatency and Interpeak Interval Values of Auditory Brainstem Response in 73 Individuals with Normal Hearing
Med Sci Monit In Press; DOI: 10.12659/MSM.937847
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292