title: Defective protein histidine phosphorylation in islets from the Goto-Kakizaki diabetic rat.
abstract: We recently described novel regulatory roles for protein histidine phosphorylation of key islet proteins (e.g., nucleoside diphosphate kinase and succinyl thiokinase) in insulin secretion from the islet beta-cell (Kowluru A. Diabetologia 44: 89-94, 2001; Kowluru A, Tannous M, and Chen HQ. Arch Biochem Biophys 398: 160-169, 2002). In this context, we also characterized a novel, ATP- and GTP-sensitive protein histidine kinase in isolated beta-cells that catalyzed the histidine phosphorylation of islet (endogenous) proteins as well as exogenously added histone 4, and we implicated this kinase in the activation of islet endogenous G proteins (Kowluru A. Biochem Pharmacol 63: 2091-2100, 2002). In the present study, we describe abnormalities in ATP- or GTP-mediated histidine phosphorylation of nucleoside diphosphate kinase in islets derived from the Goto-Kakizaki (GK) rat, a model for non-insulin-dependent diabetes. Furthermore, we provide evidence for a marked reduction in the activities of ATP- or GTP-sensitive histidine kinases in GK rat islets. On the basis of these observations, we propose that alterations in protein histidine phosphorylation could contribute toward insulin-secretory abnormalities demonstrable in the diabetic islet.
authors.affiliation: Department of Pharmaceutical Sciences, 3601 Applebaum Bldg., Wayne State University, 259 Mack Ave., Detroit, MI 48202, USA. akowluru@med.wayne.edu
authors.forename: Anjaneyulu
authors.initials: A
authors.lastname: Kowluru
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism; D006639:Histidine / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011877:Radionuclide Imaging; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar
chemical_list: D010761:Phosphorus Radioisotopes; D006639:Histidine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D009701:Nucleoside-Diphosphate Kinase