title: Simultaneous measurement of insulin sensitivity, insulin secretion, and the disposition index in conscious unhandled mice.
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.
authors.affiliation: Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA, USA. lca4@pitt.edu
authors.forename: Laura C
authors.initials: LC
authors.lastname: Alonso
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Darko
authors.initials: D
authors.lastname: Stefanovski
authors.forename: Euhan J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Srikanth
authors.initials: S
authors.lastname: Singamsetty
authors.forename: Lia C
authors.initials: LC
authors.lastname: Romano
authors.forename: Baobo
authors.initials: B
authors.lastname: Zou
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Ocaña
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Christopher P
authors.initials: CP
authors.lastname: O'Donnell
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods*; D007004:Hypoglycemic Agents / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008991:Monitoring, Physiologic; D011237:Predictive Value of Tests
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin