Diabetes
Diabetes
5 years ago

Regulation of KATPChannel Trafficking in Pancreatic β Cells by Protein Histidine Phosphorylation.

Edward Y Skolnik, William A Coetzee, Zhai Li, Charles A Stanley, Ying Sun, Chonghong Li, Jianhui Wang, Shekhar Srivastava, Irfana Soomro, Li Bao
Protein histidine phosphatase 1 (PHPT-1) is an evolutionarily conserved 14 kDa protein that dephosphorylates phosphohistidine.PHPT-1 -/- mice were generated to gain insight into the role of PHPT-1 and histidine phosphorylation/dephosphorylation in mammalian biology.PHPT-1 -/- mice exhibited neonatal hyperinsulinemic hypoglycemia due to impaired trafficking of KATPchannels to the plasma membrane in pancreatic β cells in response to low glucose and leptin and resembled patients with congenital hyperinsulinism (CHI). The defect in KATPchannel trafficking in PHPT-1-/-β cells was due to the failure of PHPT-1 to directly activate transient receptor potential channel 4 (TRPC4) resulting in decreased Ca2+influx and impaired downstream activation of AMPK. Thus, these studies demonstrate a critical role for PHPT-1 in normal pancreatic β cell function and raise the possibility that mutations in PHPT-1 and/or TRPC4 may account for yet to be defined cases of CHI.

Publisher URL: http://doi.org/10.2337/db17-1433

DOI: 10.2337/db17-1433

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