Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles
Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypo...
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fendo.2017.00330/full |
| _version_ | 1818005590223355904 |
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| author | Xuzhu Lin Lewan Parker Lewan Parker Emma Mclennan Xinmei Zhang Alan Hayes Alan Hayes Alan Hayes Glenn McConell Tara C. Brennan-Speranza Itamar Levinger Itamar Levinger |
| author_facet | Xuzhu Lin Lewan Parker Lewan Parker Emma Mclennan Xinmei Zhang Alan Hayes Alan Hayes Alan Hayes Glenn McConell Tara C. Brennan-Speranza Itamar Levinger Itamar Levinger |
| author_sort | Xuzhu Lin |
| collection | DOAJ |
| description | Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade. Extensor digitorum longus (EDL) and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204) and AS160 (Thr642) in both muscle types and increased mTOR phosphorylation (Ser2481) in EDL only. ucOC had no significant effect on the phosphorylation of AMPKα (Thr172). The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions. |
| first_indexed | 2024-04-14T04:46:08Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-14T04:46:08Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-078bb474d3044c3a8ef1442f35c055102022-12-22T02:11:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922017-11-01810.3389/fendo.2017.00330305926Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus MusclesXuzhu Lin0Lewan Parker1Lewan Parker2Emma Mclennan3Xinmei Zhang4Alan Hayes5Alan Hayes6Alan Hayes7Glenn McConell8Tara C. Brennan-Speranza9Itamar Levinger10Itamar Levinger11Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC, AustraliaInstitute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC, AustraliaSchool of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition (IPAN), Deakin University, Melbourne, VIC, AustraliaInstitute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC, AustraliaInstitute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC, AustraliaInstitute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC, AustraliaCollege of Health and Biomedicine, Victoria University, Geelong, VIC, AustraliaAustralian Institute for Musculoskeletal Science, Western Health, Melbourne, VIC, AustraliaInstitute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC, AustraliaDepartment of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, NSW, AustraliaInstitute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC, AustraliaAustralian Institute for Musculoskeletal Science, Western Health, Melbourne, VIC, AustraliaEmerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade. Extensor digitorum longus (EDL) and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204) and AS160 (Thr642) in both muscle types and increased mTOR phosphorylation (Ser2481) in EDL only. ucOC had no significant effect on the phosphorylation of AMPKα (Thr172). The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions.http://journal.frontiersin.org/article/10.3389/fendo.2017.00330/fullundercarboxylated osteocalcinskeletal muscleglucose uptakeextracellular signal-regulated kinaseadenosine monophosphate-activated protein kinasemechanistic target of rapamycin complex 2-AKT-AS160 signaling cascade |
| spellingShingle | Xuzhu Lin Lewan Parker Lewan Parker Emma Mclennan Xinmei Zhang Alan Hayes Alan Hayes Alan Hayes Glenn McConell Tara C. Brennan-Speranza Itamar Levinger Itamar Levinger Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles Frontiers in Endocrinology undercarboxylated osteocalcin skeletal muscle glucose uptake extracellular signal-regulated kinase adenosine monophosphate-activated protein kinase mechanistic target of rapamycin complex 2-AKT-AS160 signaling cascade |
| title | Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles |
| title_full | Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles |
| title_fullStr | Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles |
| title_full_unstemmed | Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles |
| title_short | Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles |
| title_sort | recombinant uncarboxylated osteocalcin per se enhances mouse skeletal muscle glucose uptake in both extensor digitorum longus and soleus muscles |
| topic | undercarboxylated osteocalcin skeletal muscle glucose uptake extracellular signal-regulated kinase adenosine monophosphate-activated protein kinase mechanistic target of rapamycin complex 2-AKT-AS160 signaling cascade |
| url | http://journal.frontiersin.org/article/10.3389/fendo.2017.00330/full |
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