Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients.
Cyclic ADP-ribose (cADPR) has been shown to be a mediator for intracellular Ca2+ mobilization for insulin secretion by glucose in pancreatic beta cells, and CD38 shows both ADP-ribosyl cyclase to synthesize cADPR from NAD+ and cADPR hydrolase to hydrolyze cADPR to ADP-ribose. We show here that 13.8% of Japanese non-insulin-dependent diabetes (NIDDM) patients examined have autoantibodies against CD38 and that the sera containing anti-CD38 autoantibodies inhibit the ADP-ribosyl cyclase activity of CD38 (P </= 0.05). Insulin secretion from pancreatic islets by glucose is significantly inhibited by the addition of the NIDDM sera with anti-CD38 antibodies (P </= 0.04-0.0001), and the inhibition of insulin secretion is abolished by the addition of recombinant CD38 (P </= 0.02). The increase of cADPR levels in pancreatic islets by glucose was also inhibited by the addition of the sera (P </= 0.05). These results strongly suggest that the presence of anti-CD38 autoantibodies in NIDDM patients can be one of the major causes of impaired glucose-induced insulin secretion in NIDDM.
Department of Biochemistry, Tohoku University School of Medicine, Sendai 980-8575, Japan.
F
F
Ikehata
J
J
Satoh
K
K
Nata
A
A
Tohgo
T
T
Nakazawa
I
I
Kato
S
S
Kobayashi
T
T
Akiyama
S
S
Takasawa
T
T
Toyota
H
H
Okamoto
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000276:immunology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009244:NAD+ Nucleosidase / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D004791:Enzyme Inhibitors; D007328:Insulin; D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498156:Cd38 protein, rat; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D005947:Glucose