Regulatory roles for nm23/nucleoside diphosphate kinase-like enzymes in insulin secretion from the pancreatic islet beta cell.
Recent studies from multiple laboratories, including our own, provided fresh insights into the contributory roles for GTP-binding proteins (G-proteins) in glucose-stimulated insulin secretion (GSIS) from the islet beta cell. However, the precise mechanisms underlying the activation of this class of signaling proteins by insulin secretagogues remain only partially understood. We recently proposed that nm23/nucleoside diphosphate kinase (NDPK) catalyzes an alternate, non-receptor-dependent activation of islet endogenous G-proteins. In further support of this proposal, we report, herein, that overexpression of wild type (WT) nm23-H1 mutant in INS cells markedly potentiated GSIS. However, an inactive mutant of nm23-H1(H118F), which is deficient in histidine kinase and NDPK activities, was considerably less effective in potentiating GSIS from these cells, suggesting that both of these activities may be relevant for the potentiating effects of nm23-H1. Potential significance of these findings in relation to contributory roles for nm23/NDPK-like enzymes in the stimulus-secretion coupling of GSIS is discussed.
Kowluru
Anjaneyulu
A
Department of Pharmaceutical Sciences, Wayne State University and beta Cell Biochemistry Laboratory, John D. Dingell VA Medical Center, Detroit, MI, 48201, USA. akowluru@med.wayne.edu
Veluthakal
Rajakrishnan
R
Kaetzel
David M
DM
D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000235:genetics*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D007328:Insulin; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase