Simultaneous measurement of insulin sensitivity, insulin secretion, and the disposition index in conscious unhandled mice.

Obesity
Laura C AlonsoChristopher P O'Donnell

Abstract

Of the parameters that determine glucose disposal and progression to diabetes in humans: first-phase insulin secretion, glucose effectiveness (Sg), insulin sensitivity (Si), and the disposition index (DI), only Si can be reliably measured in conscious mice. To determine the importance of the other parameters in murine glucose homeostasis in lean and obese states, we developed the frequently sampled intravenous glucose tolerance test (FSIVGTT) for use in unhandled mice. We validated the conscious FSIVGTT against the euglycemic clamp for measuring Si in lean and obese mice. Insulin-resistant mice had increased first-phase insulin secretion, decreased Sg, and a reduced DI, qualitatively similar to humans. Intriguingly, although insulin secretion explained most of the variation in glucose disposal in lean mice, Sg and the DI more strongly predicted glucose disposal in obese mice. DI curves identified individual diet-induced obese (DIO) mice as having compensated or decompensated insulin secretion. Conscious FSIVGTT opens the door to apply mouse genetics to the determinants of in vivo insulin secretion, Sg, and DI, and further validates the mouse as a model of metabolic disease.

References

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Citations

Jul 18, 2012·European Journal of Applied Physiology·Euhan J LeeChristopher P O'Donnell
Aug 17, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alba CarrerasDavid Gozal
Oct 3, 2013·The Journal of Clinical Investigation·Gregory J MortonMichael W Schwartz
Dec 17, 2014·Molecular Metabolism·Grace FergussonThierry Alquier
Aug 13, 2015·Molecular Metabolism·Jennifer M RojasMichael W Schwartz
Feb 1, 2017·The Journal of Endocrinology·Rebecca L HullSakeneh Zraika
Sep 3, 2014·Respiratory Physiology & Neurobiology·Mi-Kyung ShinVsevolod Y Polotsky
Jun 13, 2017·Diabetes·Jennifer D DeemMichael W Schwartz
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Nov 17, 2017·Diabetologia·Thierry Alquier, Vincent Poitout
Sep 30, 2017·CPT: Pharmacometrics & Systems Pharmacology·Oskar AlskärMaria C Kjellsson
Jun 2, 2018·Journal of Diabetes Research·Jacqueline H ParillaSakeneh Zraika
Nov 16, 2017·American Journal of Physiology. Endocrinology and Metabolism·Andreas PeterNorbert Stefan
May 16, 2013·American Journal of Physiology. Endocrinology and Metabolism·Rachel E StamaterisLaura C Alonso
Dec 10, 2017·Translational Research : the Journal of Laboratory and Clinical Medicine·Faraaz Ali ShahBryan J McVerry
Jun 15, 2021·American Journal of Physiology. Endocrinology and Metabolism·Josephine YuNeil A Youngson

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Software Mentioned

GraphPad
MinMod
GraphPad Prism

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