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Disrupted glucose homeostasis and skeletal-muscle-specific glucose uptake in an exocyst knockout mouse model.

ABSTRACT: 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 with 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.

SUBMITTER: Fujimoto BA

PROVIDER: S-EPMC8027262 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The exocyst complex regulates insulin-stimulated glucose uptake of skeletal muscle cells.

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CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle.

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Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells.

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Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice.

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| S-EPMC2886679 | biostudies-literature

Enhancement of glucose uptake in mouse skeletal muscle cells and adipocytes by P2Y6 receptor agonists.

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| S-EPMC4280206 | biostudies-literature

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