Dual Tracer Test to Measure Tissue-Specific Insulin Action in Individual Mice Identifies In Vivo Insulin Resistance Without Fasting Hyperinsulinemia.

Autor:	Cutler HB; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Madsen S; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Masson SWC; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Cooke KC; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Potter M; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Burchfield JG; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Stöckli J; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Nelson ME; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia., Cooney GJ; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia.; Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia., James DE; School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.; Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia.; Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2024 Mar 01; Vol. 73 (3), pp. 359-373.
DOI:	10.2337/db23-0035
Abstrakt:	The ability of metabolically active tissues to increase glucose uptake in response to insulin is critical to whole-body glucose homeostasis. This report describes the Dual Tracer Test, a robust method involving sequential retro-orbital injection of [14C]2-deoxyglucose ([14C]2DG) alone, followed 40 min later by injection of [3H]2DG with a maximal dose of insulin to quantify both basal and insulin-stimulated 2DG uptake in the same mouse. The collection of both basal and insulin-stimulated measures from a single animal is imperative for generating high-quality data since differences in insulin action may be misinterpreted mechanistically if basal glucose uptake is not accounted for. The approach was validated in a classic diet-induced model of insulin resistance and a novel transgenic mouse with reduced GLUT4 expression that, despite ubiquitous peripheral insulin resistance, did not exhibit fasting hyperinsulinemia. This suggests that reduced insulin-stimulated glucose disposal is not a primary contributor to chronic hyperinsulinemia. The Dual Tracer Test offers a technically simple assay that enables the study of insulin action in many tissues simultaneously. By administering two tracers and accounting for both basal and insulin-stimulated glucose transport, this assay halves the required sample size for studies in inbred mice and demonstrates increased statistical power to detect insulin resistance, relative to other established approaches, using a single tracer. The Dual Tracer Test is a valuable addition to the metabolic phenotyping toolbox. (© 2024 by the American Diabetes Association.)
Databáze:	MEDLINE
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