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CD38 autoimmunity: recent advances and relevance to human diabetes.

Authors
  • Antonelli, A
  • Ferrannini, E
Type
Published Article
Journal
Journal of endocrinological investigation
Publication Date
Jan 01, 2004
Volume
27
Issue
7
Pages
695–707
Identifiers
PMID: 15505998
Source
Medline
License
Unknown

Abstract

Human CD38 is a protein which catalyzes the synthesis of nicotinic acid adenine dinucleotide (NAADP+) and the conversion of NAD+ to cADPR. Both cADPR and NAADP+ are powerful intracellular Ca2+ ([Ca2+]i) mobilizers in different cell types. Recently, the presence of CD38 autoantibodies has been found in a significant number (9-15%) of patients with Type 2 or long-standing Type 1 diabetes. These autoantibodies are biologically active, the majority of them (-60%) displaying agonistic properties, i.e., [Ca2+]i mobilization in lymphocytic cell lines and in pancreatic islets. In cultured rat pancreatic islets, the human autoantibodies inhibit glucose-induced insulin release, whereas, in human pancreatic islets CD38 autoantibodies stimulate glucose-mediated insulin secretion. The clinical phenotype of anti-CD38-positive Type 2 diabetes differs from the LADA (latent autoimmune diabetes of adults) phenotype. When accurately matched for age and obesity, only LADA patients with anti-GAD antibodies, but not GAD-negative/ CD38-positive patients, have reduced in vivo beta-cell function in comparison to antibody-negative patients. Transgenic mice overexpressing CD38 show enhanced glucose-induced insulin release, whereas, conversely, CD38 knockout mice display a severe impairment in beta-cell function. Few Japanese diabetic patients carry a missense mutation in the CD38 gene; in Caucasian patients mutations in the CD38 gene have not been found. Collectively, these findings suggest that activation of CD38 represents an alternative signaling pathway for glucose-induced insulin secretion in human beta-cells. More information, however, is necessary to gauge the role of CD38 autoimmunity in the context of the natural history of human Type 1 or Type 2 diabetes.

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