Significance of ecto-cyclase activity of CD38 in insulin secretion of mouse pancreatic islet cells.
Cyclic ADP-ribose (cADPR), a product of CD38, has a second messenger role for in intracellular Ca(2+) mobilization from microsomes of pancreatic islets as well as from a variety of other cells. ADP-ribosylation of CD38 by ecto-mono ADP-ribosyltransferase in activated T cells results in apoptosis as well as inactivation of its activities. We, therefore, examined the effect of ADP-ribosylation of CD38 in mouse pancreatic islet cells. NAD-dependent inactivation and ADP-ribosylation of CD38, intracellular concentrations of cADPR and Ca(2+), and insulin secretion were measured following incubation of mouse pancreatic islet cells with NAD. ADP-ribosylation of CD38 inactivated its ecto-enzyme activities, and abolished glucose-induced increase of cADPR production, intracellular concentration of Ca(2+), and insulin secretion. Taken together, ecto-cyclase activity of CD38 to produce intracellular cADPR seems to be indispensable for insulin secretion.
An
N H
NH
Department of Biochemistry, Chonbuk National University Medical School, Chonju, 561-182, Korea.
Han
M K
MK
Um
C
C
Park
B H
BH
Park
B J
BJ
Kim
H K
HK
Kim
U H
UH
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D036563:Cyclic ADP-Ribose; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009243:NAD / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors / Q000502:physiology*; D015290:Second Messenger Systems
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007328:Insulin; D008562:Membrane Glycoproteins; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1