Dataset Information

Autonomous interconversion between adult pancreatic ?-cells and ?-cells after differential metabolic challenges.

ABSTRACT:

Background

Evidence hints at the ability of ?-cells to emerge from non-?-cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous ?-cell regeneration without genetic or pharmacological manipulations remain to be determined.

Methods & results

Using PANIC-ATTAC mice, a model of titratable, acute ?-cell apoptosis capable of autonomous, and effective islet mass regeneration, we demonstrate that an extended washout of residual tamoxifen activity is crucial for ?-cell lineage tracing studies using the tamoxifen-inducible Cre/loxP systems. We further establish a doxycycline-inducible system to label different cell types in the mouse pancreas and pursued a highly quantitative assessment to trace adult ?-cells after various metabolic challenges. Beyond proliferation of pre-existing ?-cells, non-?-cells contribute significantly to the post-challenge regenerated ?-cell pool. ?-cell trans-differentiation is the predominant mechanism upon post-apoptosis regeneration and multiparity. No contributions from exocrine acinar cells were observed. During diet-induced obesity, about 25% of ?-cells arise de novo from ?-cells. Ectopic expression of Nkx6.1 promotes ?-to-? conversion and insulin production.

Conclusions

We identify the origins and fates of adult ?-cells upon post-challenge upon autonomous regeneration of islet mass and establish the quantitative contributions of the different cell types using a lineage tracing system with high temporal resolution.

SUBMITTER: Ye R

PROVIDER: S-EPMC4921793 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Autonomous interconversion between adult pancreatic α-cells and β-cells after differential metabolic challenges.

Ye Risheng R Wang Miao M Wang Qiong A QA Spurgin Stephen B SB Wang Zhao V ZV Sun Kai K Scherer Philipp E PE

Molecular metabolism 20160510 7

<h4>Background</h4>Evidence hints at the ability of β-cells to emerge from non-β-cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous β-cell regeneration without genetic or pharmacological manipulations remain to be determined.<h4>Methods & results</h4>Using PANIC-ATTAC mice, a model of titratable, acute β-cell apoptosis capable of autonomous, and effective islet mass regeneration, we demonstrate that an extended washout of r ...[more]

PMID: 27408770

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