Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients

J Clin Invest. 1998 Jul 15;102(2):395-401. doi: 10.1172/JCI1656.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Adenosine Diphosphate Ribose / analogs & derivatives
  • Adenosine Diphosphate Ribose / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, CD*
  • Antigens, Differentiation / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Autoantibodies / metabolism*
  • Cyclic ADP-Ribose
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Enzyme Inhibitors / immunology
  • Enzyme Inhibitors / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • NAD+ Nucleosidase / immunology*
  • Rats
  • Rats, Wistar

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Autoantibodies
  • Enzyme Inhibitors
  • Insulin
  • Membrane Glycoproteins
  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • Cd38 protein, rat
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1
  • Glucose