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Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals
La Jolla Inst Allergy & Immunol, Type Diabet Ctr 1, La Jolla, CA 92037 USA.
La Jolla Inst Allergy & Immunol, Type Diabet Ctr 1, La Jolla, CA 92037 USA.
La Jolla Inst Allergy & Immunol, Type Diabet Ctr 1, La Jolla, CA 92037 USA.
St Vincents Inst, Dept Immunol & Diabet, Melbourne, Vic 3065, Australia.
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2011 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 27, no 8, 746-754 p.Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

BACKGROUND: Recent reports have established the notion that many patients with longstanding type 1 diabetes (T1D) possess a remnant population of insulin-producing beta cells. It remains questionable, however, whether these surviving cells can physiologically sense and respond to glucose stimuli.

METHODS: Frozen pancreatic sections from non-diabetic donors (n=8), type 2 diabetic patients (n=4), islet autoantibody-positive non-diabetic patients (n=3), type 1 diabetic patients (n=10) and one case of gestational diabetes were obtained via the network for Pancreatic Organ Donors. All longstanding T1D samples were selected based on the detection of insulin-producing beta cells in the pancreas by immunohistochemistry. RNA was isolated from all sections followed by cDNA preparation and quantitative real-time polymerase chain reaction for insulin, glucose transporter 1 (GLUT1), GLUT2 and GLUT3. Finally, immunofluorescent staining was performed on consecutive sections for all four of these markers and a comparison was made between the expression of GLUT2 in humans versus NOD mice.

RESULTS: In contrast to islets from the most widely used T1D model, the NOD mouse, human islets predominantly express GLUT1 and, to a much lesser extent, GLUT3 on their surface instead of GLUT2. Relative expression levels of these receptors do not significantly change in the context of the various (pre-)diabetic conditions studied. Moreover, in both species preservation of GLUT expression was observed even under conditions of substantial leucocyte infiltration or decades of T1D duration.

CONCLUSIONS: These data suggest that despite being subjected to multiple years of physiological stress, the remaining beta-cell population in longstanding T1D patients retains a capacity to sense glucose via its GLUTs.

Place, publisher, year, edition, pages
2011. Vol. 27, no 8, 746-754 p.
Keyword [en]
glucose transporters; type 1 diabetes; beta cells; pancreas; islets of Langerhans; insulin
National Category
Clinical Laboratory Medicine
Identifiers
URN: urn:nbn:se:uu:diva-304613DOI: 10.1002/dmrr.1246ISI: 000300108000005PubMedID: 22069254OAI: oai:DiVA.org:uu-304613DiVA: diva2:1033210
Available from: 2016-10-06 Created: 2016-10-06 Last updated: 2017-11-30Bibliographically approved
In thesis
1. Immunopathology of the Pancreas in Type 1 Diabetes
Open this publication in new window or tab >>Immunopathology of the Pancreas in Type 1 Diabetes
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 1 diabetes (T1D) results from a loss of functional insulin-producing pancreatic beta cells. The etiology of T1D is poorly understood, but the detection of infiltrating inflammatory cells in the pancreas and circulating autoantibodies has led to the common notion that an autoimmune process plays a central role in the pathogenesis of the disease.

The aim of this doctoral thesis was to assess various aspects of the immunopathology of type 1 diabetes. To this purpose, studies have been conducted on pancreatic material from the Network for Pancreatic Organ Donors with Diabetes (nPOD) collection, the Nordic Network for Islet Transplantation, and the Diabetes Virus Detection (DiViD) study.

Paper I is a study on pancreatic tissue from organ donors with varying duration of T1D as well as non-diabetic donors and subjects with other types of diabetes, in which persistent expression of glucose transporters was shown on the beta cell membrane despite several years of T1D. Glucose transporter 1 was also confirmed as the predominant glucose transporter on human pancreatic islets. In paper II, we report on signs of inflammation in the exocrine but not in the endocrine pancreas in non-diabetic organ donors with diabetes-related autoantibodies, suggesting that diabetes-associated autoantibodies can occur in response to unspecific pancreatic lesions.

Paper III aimed to characterize the T cell-infiltration of pancreatic islets in material from recent-onset T1D patients. Insulitis was shown in all subjects, but with distinct differences in expression analysis of T- and B cell activation to cell-mediated allorejected kidney transplant. Also Paper IV was conducted on material from recent-onset cases and showed increased islet glucagon content, in combination with a reduced number of islets but sustained mean islet size.

Together, these results provide expansion of our knowledge of the immunopathology in T1D, and will hopefully assist in bringing us towards a deeper understanding of T1D aetiology and eventually an effective cure.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 53 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1263
Keyword
Type 1 diabetes, glucagon, T cells, autoantibodies, glucose transporters, islets of Langerhans, pancreas
National Category
Endocrinology and Diabetes Immunology in the medical area
Research subject
Clinical Immunology
Identifiers
urn:nbn:se:uu:diva-304621 (URN)978-91-554-9711-8 (ISBN)
Public defence
2016-11-24, Rudbecksalen, Dag Hammarskjölds väg 20, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2016-11-01 Created: 2016-10-06 Last updated: 2016-11-02

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