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Intolerable secretion and diabetes in tolerant transgenic mice, revisited

A new mouse model linking diabetes, insulin secretion and autoimmunity with a high-fat diet supports a shared mechanism for type 1 (T1D) and type 2 (T2D) diabetes. In this model, the protein secretion system of insulin-producing pancreatic beta cells is stressed, leading to increased beta cell apoptosis and diabetes via reduced levels of the transcription factor GLIS3, a pathogenic pathway that can be mimicked by a high-fat diet.

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Figure 1: Reduced GLIS3 function or a high-fat diet can compromise pancreatic islet beta cell mass and insulin secretion via ER stress, overload of the UPR and increased beta cell apoptosis to such an extent that diabetes develops.


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Correspondence to John A Todd.

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Todd, J. Intolerable secretion and diabetes in tolerant transgenic mice, revisited. Nat Genet 48, 476–477 (2016).

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