Our data show the aberrant mTORC1 activity in islets from patients with type 2 diabetes, in human islets cultured under diabetes-associated increased glucose conditions and in diabetic mouse islets. This suggests that elevated mTORC1 activation is a striking pathogenic hallmark of islets in type 2 diabetes, contributing to impaired beta cell function and survival in the presence of metabolic stress.

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Highlights d PHLPP1/2 are highly elevated in metabolically stressed b cells in diabetes d Metabolic-stress-induced mTORC1 hyper-activation leads to PHLPP upregulation d PHLPPs regulate b-cell survival-dependent kinases AKT and MST1 d PHLPP inhibition restores glycemia, b-cell survival, and function

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