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Glucose Effectiveness: The Mouse Trap in the Development of Novel beta-Cell Replacement Therapies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
2016 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 100, no 1, 111-115 p.Article in journal (Refereed) Published
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Abstract [en]

Background Cure of diabetes and normalization of glucose disposal during intravenous glucose tolerance tests (IVGTT) remains critical for stringent evaluation of novel replacement therapies in type 1 diabetes. Glucose disposal during an IVGTT depends on a complex interaction of both insulin-dependent and -independent mechanisms. Glucose effectiveness, that is, the function of glucose per se, independent of insulin, to stimulate its uptake and suppress endogenous glucose production is less recognized. Methods To unravel the relative importance of these pathways, rats were injected with streptozotocin to induce diabetes and implanted subcutaneously with slow-release devices of insulin. Results These animals demonstrated rapid normalization of blood glucose and perfectly normal glucose disposal during an IVGTT with no differences when compared with nondiabetic controls even though no active c-peptide secretion was detected in plasma and almost no remaining insulin-producing cells were present in the pancreas. Conclusions The present study highlights that glucose is the predominant mediator of its own disposal in rodents having only basal and nonglucose-regulated plasma insulin levels. The herein presented results calls for a reassessment how results obtained in the most commonly used experimental models should be interpreted in the development of future replacement therapies in type 1 diabetes.

Place, publisher, year, edition, pages
2016. Vol. 100, no 1, 111-115 p.
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Immunology in the medical area
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URN: urn:nbn:se:uu:diva-276874DOI: 10.1097/TP.0000000000000900ISI: 000367989600003PubMedID: 26413992OAI: oai:DiVA.org:uu-276874DiVA: diva2:903705
Funder
Novo NordiskSwedish Child Diabetes FoundationEU, FP7, Seventh Framework Programme, HEALTH-F4-2013-602889Swedish Diabetes Association
Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2017-11-30Bibliographically approved

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Korsgren, Olle

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