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α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes.

Cell reports | 2018

Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of α-to-β cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia.

Pubmed ID: 29514095 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK090570
  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK104211
  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK108120
  • Agency: NIH HHS, United States
    Id: S10 OD021630
  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK112232
  • Agency: NIDDK NIH HHS, United States
    Id: U01 DK089572
  • Agency: NIDDK NIH HHS, United States
    Id: F30 DK118830
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK097829
  • Agency: NIDDK NIH HHS, United States
    Id: R21 DK066636
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007347
  • Agency: BLRD VA, United States
    Id: I01 BX000666
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK094199
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020593
  • Agency: NIDDK NIH HHS, United States
    Id: R24 DK106755
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK050203

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This is a list of tools and resources that we have found mentioned in this publication.


Integrated Islet Distribution Program (IIDP) (tool)

RRID:SCR_014387

The goal of the Integrated Islet Distribution Program (IIDP) is to work with the leading islet isolation centers in the U.S. to distribute high quality human islets to the diabetes research community, in order to advance scientific discoveries and translational medicine.

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Network for Pancreatic Organ Donors with Diabetes (tool)

RRID:SCR_014641

A collaborative research project that supports nPOD approved diabetes investigators by freely providing rare and difficult-to-obtain tissues from type 1 and type 2 diabetes donors. Interested researchers are encouraged to apply to obtain nPOD tissues, or to request access to analyze cases in the nPOD Online Pathology site. Interested donors can contact nPOD directly for more information.

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ANOVA (software resource)

RRID:SCR_002427

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on April 12,2023. Matlab code for two-factor (location and year) analysis-of-variance model for the calculation of climate anomalies, in which the reference interval is specified as the full length of the dataset. This scheme avoids the affects of shorter (e.g. 1961-1990) reference intervals on the temporal evolution of the spatial standard deviation of climate anomalies. Data files provided.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Human Islet Research Network (HIRN) (data or information resource)

RRID:SCR_014393

Network helps to organize and support collaborative research related to loss of functional beta cell mass in Type 1 Diabetes (T1D). Project consists of four independent research initiatives: Consortium on Beta Cell Death and Survival (CBDS), Consortium on Human Islet Biomimetics (CHIB), Consortium on Modeling Autoimmune Interactions (CMAI), Consortium on Targeting and Regeneration (CTAR), and Human Pancreas Analysis Program (HPAP).

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