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PTPN2 regulates metabolic flux to affect beta cell susceptibility to inflammatory stress

ABSTRACT: Protein tyrosine phosphatase N2 (Ptpn2) is a type 1 diabetes (T1D) candidate gene identified from human genome-wide association studies. PTPN2 is highly expressed in human and murine islets and becomes elevated upon inflammation, suggesting that PTPN2 may be important for beta cell survival in the context of T1D. To test whether PTPN2 contributed to beta cell dysfunction in an inflammatory environment, we generated a beta cell-specific deletion of Ptpn2 in mice (Ptpn2 βKO). While unstressed animals exhibit normal metabolic profiles, streptozotocin (STZ) Ptpn2 βKO mice display marked increase in hyperglycemia and death due to exacerbated beta cell loss. Furthermore, cytokine treated Ptpn2 KO islets resulted in mitochondrial defects and reduced glucose-induced metabolic flux, suggesting beta cells lacking Ptpn2 are more susceptible to inflammatory stress associated with T1D due to compromised metabolic fitness.

ORGANISM(S): Mus musculus

PROVIDER: GSE215852 | GEO | 2023/12/01

REPOSITORIES: GEO

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