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Use of the hyperinsulinemic euglycemic clamp to assess insulin sensitivity in guinea pigs: dose response, partitioned glucose metabolism, and species comparisons
journal contribution
posted on 2017-07-01, 00:00 authored by Dane M Horton, David A Saint, Julie OwensJulie Owens, Kathryn L Gatford, Karen L KindThe guinea pig is an alternate small animal model for the study of metabolism, including insulin sensitivity. However, only one study to date has reported the use of the hyperinsulinemic euglycemic clamp in anesthetized animals in this species, and the dose response has not been reported. We therefore characterized the dose-response curve for whole body glucose uptake using recombinant human insulin in the adult guinea pig. Interspecies comparisons with published data showed species differences in maximal whole body responses (guinea pig ≈ human < rat < mouse) and the insulin concentrations at which half-maximal insulin responses occurred (guinea pig > human ≈ rat > mouse). In subsequent studies, we used concomitant d-[3-3H]glucose infusion to characterize insulin sensitivities of whole body glucose uptake, utilization, production, storage, and glycolysis in young adult guinea pigs at human insulin doses that produced approximately half-maximal (7.5 mU·min-1·kg-1) and near-maximal whole body responses (30 mU·min-1·kg-1). Although human insulin infusion increased rates of glucose utilization (up to 68%) and storage and, at high concentrations, increased rates of glycolysis in females, glucose production was only partially suppressed (~23%), even at high insulin doses. Fasting glucose, metabolic clearance of insulin, and rates of glucose utilization, storage, and production during insulin stimulation were higher in female than in male guinea pigs (P < 0.05), but insulin sensitivity of these and whole body glucose uptake did not differ between sexes. This study establishes a method for measuring partitioned glucose metabolism in chronically catheterized conscious guinea pigs, allowing studies of regulation of insulin sensitivity in this species.
History
Journal
American journal of physiology: regulatory, integrative and comparative physiologyVolume
313Issue
1Pagination
R19 - R28Publisher
American Physiological SocietyLocation
Bethesda, Md.Publisher DOI
Link to full text
ISSN
0363-6119eISSN
1522-1490Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2017 the American Physiological SocietyUsage metrics
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guinea piginsulin sensitivitysex differencesspecies differencesAnimalsBlood GlucoseDose-Response Relationship, DrugFemaleGlucoseGlucose Clamp TechniqueGuinea PigsHumansInsulin ResistanceInsulin, Regular, PorkMaleSpecies SpecificityScience & TechnologyLife Sciences & BiomedicinePhysiologySUBCUTANEOUS ADIPOSE-TISSUEGROWTH-FACTOR-IDIABETES-MELLITUSLITTER SIZEGLYCOGEN-SYNTHASEANIMAL-MODELRESISTANCERATSOBESITYRESPONSIVENESS
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