Program in Molecular Medicine; Division of Endocrinology, Metabolism and Diabetes, Department of Medicine
Biochemistry | Endocrine System Diseases | Endocrinology | Endocrinology, Diabetes, and Metabolism | Molecular Biology | Musculoskeletal, Neural, and Ocular Physiology | Nutritional and Metabolic Diseases
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.
diabetes, exocyst complex, glucose transporter, insulin resistance, skeletal muscle
Rights and Permissions
© 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/).
DOI of Published Version
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
The Journal of biological chemistry
Fujimoto BA, Young M, Nakamura N, Ha H, Carter L, Pitts MW, Torres D, Noh HL, Suk S, Kim JK, Polgar N. (2021). Disrupted glucose homeostasis and skeletal muscle-specific glucose uptake in an exocyst knockout mouse model. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.jbc.2021.100482. Retrieved from https://escholarship.umassmed.edu/oapubs/4605
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Biochemistry Commons, Endocrine System Diseases Commons, Endocrinology Commons, Endocrinology, Diabetes, and Metabolism Commons, Molecular Biology Commons, Musculoskeletal, Neural, and Ocular Physiology Commons, Nutritional and Metabolic Diseases Commons