Transient Changes in Four GLUT4 Compartments in Rat Adipocytes during the Transition Insulin-Stimulated To Basal: Implications for the GLUT4 Trafficking Pathway

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• 作者：J. S. Hah ; J. W. Ryu ; W. Lee ; B. S. Kim ; M. Lachaal ; R. A. Spangler ; and C. Y. Jung
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：December 3, 2002
• 年：2002
• 卷：41
• 期：48
• 页码：14364 - 14371
• 全文大小：146K
• 年卷期：v.41,no.48(December 3, 2002)
• ISSN：1520-4995

文摘

In rat adipocytes, insulin-induced GLUT4 recruitment to the plasma membrane (PM) isassociated with characteristic changes in the GLUT4 contents of three distinct endosomal fractions, T, H,and L. The organelle-specific marker distribution pattern suggests that these endosomal GLUT4compartments are sorting endosomes (SR), GLUT4-storage endosomes (ST), and GLUT4 exocytoticvesicules (EV), respectively, prompting us to analyze GLUT4 recycling based upon a four-compartmentkinetic model. Our analysis revealed that insulin modulates GLUT4 trafficking at multiple steps, includingnot only the endocytotic and exocytotic rates, but also the two rate coefficients coupling the threeintracellular compartments. This analysis assumes that GLUT4 cycles through PM T, H,L, and back toPM, in that order, with transitions characterized by four first-order coefficients. Values assigned to thesecoefficients are based upon the four steady-state GLUT4 pool sizes assessed under both basal and insulinstimulated states and the transition time courses observed in the plasma membrane GLUT4 pool. Herewe present the first reported experimental measurements of transient changes in each of the four GLUT4compartments during the insulin-stimulated to basal transition in rat adipocytes and compare theseexperimental results with the corresponding model simulations. The close correlation of these resultsoffers clear support for the general validity of the assumed model structure and the assignment of the Tcompartment to the sorting endosome GLUT4 pool. Variations in the recycling pathway from that of anunbranched cyclic topography are also considered in the light of these experimental observations. Thepossibility that H is a coupled GLUT4 storage compartment lying outside the direct cyclic pathway iscontraindicated by the data. Okadaic acid-induced GLUT4 recruitment is accompanied by modulation ofthe rate coefficients linking individual endosomal GLUT4 compartments, further demonstrating a significantrole of the endosomal pathways in GLUT4 exocytosis.