GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability
Abstract Background Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impair...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-04-01
|
| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-024-02079-z |
| _version_ | 1797219596109873152 |
|---|---|
| author | J. S. Barrett J. A. Strauss L. S. Chow S. O. Shepherd A. J. M. Wagenmakers Y. Wang |
| author_facet | J. S. Barrett J. A. Strauss L. S. Chow S. O. Shepherd A. J. M. Wagenmakers Y. Wang |
| author_sort | J. S. Barrett |
| collection | DOAJ |
| description | Abstract Background Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impaired proximal insulin signalling. Whether GLUT4 localisation to the plasma membrane is subsequently affected by elevated FFA availability is not known. Methods Trained (n = 11) and sedentary (n = 10) individuals, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed for GLUT4 membrane localisation and microvesicle size and distribution using immunofluorescence microscopy. Results At baseline, trained individuals had more small GLUT4 spots at the plasma membrane, whereas sedentary individuals had larger GLUT4 spots. GLUT4 localisation with the plasma membrane increased at 2 h (P = 0.04) of the hyperinsulinemic-euglycemic clamp, and remained elevated until 6 h, with no differences between groups or infusion type. The number of GLUT4 spots was unchanged at 2 h of infusion. However, from 2 to 6 h there was a decrease in the number of small GLUT4 spots at the plasma membrane (P = 0.047), with no differences between groups or infusion type. Conclusion GLUT4 localisation with the plasma membrane increases during a hyperinsulinemic-euglycemic clamp, but this is not altered by elevated FFA availability. GLUT4 appears to disperse from small GLUT4 clusters located at the plasma membrane to support glucose uptake during a hyperinsulinaemic-euglycaemic clamp. |
| first_indexed | 2024-04-24T12:36:09Z |
| format | Article |
| id | doaj.art-67c84133a96c4a4b8e1a5353ab8b87e9 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-24T12:36:09Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-67c84133a96c4a4b8e1a5353ab8b87e92024-04-07T11:28:51ZengBMCLipids in Health and Disease1476-511X2024-04-0123111310.1186/s12944-024-02079-zGLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availabilityJ. S. Barrett0J. A. Strauss1L. S. Chow2S. O. Shepherd3A. J. M. Wagenmakers4Y. Wang5Research Institute for Sport & Exercise Sciences, Liverpool John Moores UniversityResearch Institute for Sport & Exercise Sciences, Liverpool John Moores UniversityDepartment of Medicine, University of MinnesotaResearch Institute for Sport & Exercise Sciences, Liverpool John Moores UniversityResearch Institute for Sport & Exercise Sciences, Liverpool John Moores UniversityDiscovery Sciences, AstraZeneca R&D, Cambridge Science ParkAbstract Background Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impaired proximal insulin signalling. Whether GLUT4 localisation to the plasma membrane is subsequently affected by elevated FFA availability is not known. Methods Trained (n = 11) and sedentary (n = 10) individuals, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed for GLUT4 membrane localisation and microvesicle size and distribution using immunofluorescence microscopy. Results At baseline, trained individuals had more small GLUT4 spots at the plasma membrane, whereas sedentary individuals had larger GLUT4 spots. GLUT4 localisation with the plasma membrane increased at 2 h (P = 0.04) of the hyperinsulinemic-euglycemic clamp, and remained elevated until 6 h, with no differences between groups or infusion type. The number of GLUT4 spots was unchanged at 2 h of infusion. However, from 2 to 6 h there was a decrease in the number of small GLUT4 spots at the plasma membrane (P = 0.047), with no differences between groups or infusion type. Conclusion GLUT4 localisation with the plasma membrane increases during a hyperinsulinemic-euglycemic clamp, but this is not altered by elevated FFA availability. GLUT4 appears to disperse from small GLUT4 clusters located at the plasma membrane to support glucose uptake during a hyperinsulinaemic-euglycaemic clamp.https://doi.org/10.1186/s12944-024-02079-zLipid infusionGLUT4 translocationSkeletal muscle |
| spellingShingle | J. S. Barrett J. A. Strauss L. S. Chow S. O. Shepherd A. J. M. Wagenmakers Y. Wang GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability Lipids in Health and Disease Lipid infusion GLUT4 translocation Skeletal muscle |
| title | GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability |
| title_full | GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability |
| title_fullStr | GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability |
| title_full_unstemmed | GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability |
| title_short | GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability |
| title_sort | glut4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability |
| topic | Lipid infusion GLUT4 translocation Skeletal muscle |
| url | https://doi.org/10.1186/s12944-024-02079-z |
| work_keys_str_mv | AT jsbarrett glut4localisationwiththeplasmamembraneisunaffectedbyanincreaseinplasmafreefattyacidavailability AT jastrauss glut4localisationwiththeplasmamembraneisunaffectedbyanincreaseinplasmafreefattyacidavailability AT lschow glut4localisationwiththeplasmamembraneisunaffectedbyanincreaseinplasmafreefattyacidavailability AT soshepherd glut4localisationwiththeplasmamembraneisunaffectedbyanincreaseinplasmafreefattyacidavailability AT ajmwagenmakers glut4localisationwiththeplasmamembraneisunaffectedbyanincreaseinplasmafreefattyacidavailability AT ywang glut4localisationwiththeplasmamembraneisunaffectedbyanincreaseinplasmafreefattyacidavailability |