Barrett, JS, Strauss, JA, Chow, LS, Shepherd, SO, Wagenmakers, AJM and Wang, Y (2024) GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability. Lipids in Health and Disease, 23 (1). pp. 1-13. ISSN 1476-511X

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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.

Item Type:	Article
Uncontrolled Keywords:	Muscle, Skeletal; Cell Membrane; Humans; Insulin; Glucose; Fatty Acids, Nonesterified; Glucose Transporter Type 4; GLUT4 translocation; Lipid infusion; Skeletal muscle; Humans; Fatty Acids, Nonesterified; Glucose; Muscle, Skeletal; Insulin; Cell Membrane; Glucose Transporter Type 4; 0899 Other Information and Computing Sciences; 1101 Medical Biochemistry and Metabolomics; 1111 Nutrition and Dietetics; Nutrition & Dietetics
Subjects:	T Technology > TX Home economics > TX341 Nutrition. Foods and food supply Q Science > QP Physiology R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport & Exercise Sciences
Publisher:	BioMed Central
SWORD Depositor:	A Symplectic
Date Deposited:	08 Apr 2024 14:54
Last Modified:	08 Apr 2024 15:00
DOI or ID number:	10.1186/s12944-024-02079-z
URI:	https://researchonline.ljmu.ac.uk/id/eprint/22980

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