Disrupted glucose homeostasis and skeletal muscle-specific glucose uptake in an exocyst knockout mouse model
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Authors
Fujimoto, Brent A.Young, Madison
Nakamura, Nicole
Ha, Herena
Carter, Lamar
Pitts, Matthew W.
Torres, Daniel
Noh, Hye Lim
Suk, Sujin
Kim, Jason K.
Polgar, Noemi
UMass Chan Affiliations
Division of Endocrinology, Metabolism and Diabetes, Department of MedicineProgram in Molecular Medicine
Document Type
Journal ArticlePublication Date
2021-02-26Keywords
diabetesexocyst complex
glucose transporter
insulin resistance
skeletal muscle
Biochemistry
Endocrine System Diseases
Endocrinology
Endocrinology, Diabetes, and Metabolism
Molecular Biology
Musculoskeletal, Neural, and Ocular Physiology
Nutritional and Metabolic Diseases
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Show full item recordAbstract
Skeletal muscle is responsible for the majority of glucose disposal following meals, and this is achieved by insulin-mediated trafficking of glucose transporter type 4 (GLUT4) to the cell membrane. The eight-protein exocyst trafficking complex facilitates targeted docking of membrane-bound vesicles, a process underlying the regulated delivery of fuel transporters. We previously demonstrated the role of exocyst subunit EXOC5 in insulin-stimulated GLUT4 exocytosis and glucose uptake in cultured rat skeletal myoblasts. However, the in vivo role of EXOC5 in skeletal muscle remains unclear. Using mice with inducible, skeletal muscle-specific knockout of exocyst subunit EXOC5 (Exoc5-SMKO), we examined how muscle-specific disruption of the exocyst would affect glucose homeostasis in vivo. We found that both male and female Exoc5-SMKO mice displayed elevated fasting glucose levels. Additionally, male Exoc5-SMKO mice had impaired glucose tolerance and lower serum insulin levels. Using indirect calorimetry, we observed that male Exoc5-SMKO mice have a reduced respiratory exchange ratio during the light period and lower energy expenditure. Using the hyperinsulinemic-euglycemic clamp method, we further showed that insulin-stimulated skeletal muscle glucose uptake is reduced in Exoc5-SMKO males compared to wild-type controls. Overall, our findings indicate that EXOC5 and the exocyst are necessary for insulin-stimulated glucose uptake in skeletal muscle and regulate glucose homeostasis in vivo.Source
Fujimoto BA, Young M, Nakamura N, Ha H, Carter L, Pitts MW, Torres D, Noh HL, Suk S, Kim JK, Polgar N. Disrupted glucose homeostasis and skeletal muscle-specific glucose uptake in an exocyst knockout mouse model. J Biol Chem. 2021 Feb 26;296:100482. doi: 10.1016/j.jbc.2021.100482. Epub ahead of print. PMID: 33647317; PMCID: PMC8027262. Link to article on publisher's site
DOI
10.1016/j.jbc.2021.100482Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41803PubMed ID
33647317Related Resources
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© 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.jbc.2021.100482
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Except where otherwise noted, this item's license is described as © 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).