Defective protein histidine phosphorylation in islets from the Goto-Kakizaki diabetic rat.
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.
Kowluru
Anjaneyulu
A
Department of Pharmaceutical Sciences, 3601 Applebaum Bldg., Wayne State University, 259 Mack Ave., Detroit, MI 48202, USA. akowluru@med.wayne.edu
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
D010761:Phosphorus Radioisotopes; D006639:Histidine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D009701:Nucleoside-Diphosphate Kinase