| First Author | Srivastava S | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 5 | Pages | 849-860 |
| PubMed ID | 29440278 | Mgi Jnum | J:262099 |
| Mgi Id | MGI:6152889 | Doi | 10.2337/db17-1433 |
| Citation | Srivastava S, et al. (2018) Regulation of KATP Channel Trafficking in Pancreatic beta-Cells by Protein Histidine Phosphorylation. Diabetes 67(5):849-860 |
| abstractText | 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 KATP channels to the plasma membrane in pancreatic beta-cells in response to low glucose and leptin and resembled patients with congenital hyperinsulinism (CHI). The defect in KATP channel trafficking in PHPT-1(-/-) beta-cells was due to the failure of PHPT-1 to directly activate transient receptor potential channel 4 (TRPC4), resulting in decreased Ca(2+) influx and impaired downstream activation of AMPK. Thus, these studies demonstrate a critical role for PHPT-1 in normal pancreatic beta-cell function and raise the possibility that mutations in PHPT-1 and/or TRPC4 may account for yet to be defined cases of CHI. |
