ArticleDiabetes2009
Dynamic changes in pancreatic endocrine cell abundance, distribution, and function in antigen-induced and spontaneous autoimmune diabetes.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- The phosphatidylserine flippase β-subunit Tmem30a is essential for normal insulin maturation and secretion.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes.Frontiers in immunology · 2021Article
- Allograft inflammatory factor-1 in myeloid cells drives autoimmunity in type 1 diabetes.JCI insight · 2020Article
- Characterization of Islet Leukocyte Populations in Human and Murine Islets by Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Associations of serum glucagon levels with glycemic variability in type 1 diabetes with different disease durations.Endocrine · 2018Article
- Short-term changes in pancreatic α-cell function after the onset of fulminant type 1 diabetes.Journal of diabetes investigation · 2018Article
- IRE1-XBP1 pathway regulates oxidative proinsulin folding in pancreatic β cells.The Journal of cell biology · 2018Article
- Biphasic decline of β-cell function with age in euglycemic nonobese diabetic mice parallels diabetes onset.IUBMB life · 2015Article
- Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice.Immunology · 2015Article
- Islet remodeling in female mice with spontaneous autoimmune and streptozotocin-induced diabetes.PloS one · 2014Article
- Diminished adenosine A1 receptor expression in pancreatic α-cells may contribute to the pathology of type 1 diabetes.Diabetes · 2013Article
- TGF-β superfamily member Nodal stimulates human β-cell proliferation while maintaining cellular viability.Endocrinology · 2013Article
- Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition.Diabetologia · 2012Article
- Metabolic function of a suboptimal transplanted islet mass in nonhuman primates on rapamycin monotherapy.Cell transplantation · 2012Article
- Article
- Insulin reciprocally regulates glucagon secretion in humans.Diabetes · 2010Article
- Multiple endocrine neoplasia type 1 deletion in pancreatic alpha-cells leads to development of insulinomas in mice.Endocrinology · 2010Article
- Pancreatic beta cells require NeuroD to achieve and maintain functional maturity.Cell metabolism · 2010Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveInsulin deficiency in type 1 diabetes and in rodent autoimmune diabetes models is caused by beta-cell-specific killing by autoreactive T-cells. Less is known about beta-cell numbers and phenotype remaining at diabetes onset and the fate of other pancreatic endocrine cellular constituents. RESEARCH DESIGN AND
methodsWe applied multicolor flow cytometry, confocal microscopy, and immunohistochemistry, supported by quantitative RT-PCR, to simultaneously track pancreatic endocrine cell frequencies and phenotypes during a T-cell-mediated beta-cell-destructive process using two independent autoimmune diabetes models, an inducible autoantigen-specific model and the spontaneously diabetic NOD mouse.
resultsThe proportion of pancreatic insulin-positive beta-cells to glucagon-positive alpha-cells was about 4:1 in nondiabetic mice. Islets isolated from newly diabetic mice exhibited the expected severe beta-cell depletion accompanied by phenotypic beta-cell changes (i.e., hypertrophy and degranulation), but they also revealed a substantial loss of alpha-cells, which was further confirmed by quantitative immunohistochemisty. While maintaining normal randomly timed serum glucagon levels, newly diabetic mice displayed an impaired glucagon secretory response to non-insulin-induced hypoglycemia.
conclusionsSystematically applying multicolor flow cytometry and immunohistochemistry to track declining beta-cell numbers in recently diabetic mice revealed an altered endocrine cell composition that is consistent with a prominent and unexpected islet alpha-cell loss. These alterations were observed in induced and spontaneous autoimmune diabetes models, became apparent at diabetes onset, and differed markedly within islets compared with sub-islet-sized endocrine cell clusters and among pancreatic lobes. We propose that these changes are adaptive in nature, possibly fueled by worsening glycemia and regenerative processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.