Authors: A Antonelli E Ferrannini
Publish Date: 2014/04/02
Volume: 27, Issue: 7, Pages: 695-707
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 longstanding Type 1 diabetes These autoantibodies are biologically active the majority of them ∼60 displaying agonistic properties ie Ca2+i mobilization in lymphocytic cell lines and in pancreatic islets In cultured rat pancreatic islets the human autoantibodies inhibit glucoseinduced insulin release whereas in human pancreatic islets CD38 autoantibodies stimulate glucosemediated insulin secretion The clinical phenotype of antiCD38positive Type 2 diabetes differs from the LADA latent autoimmune diabetes of adults phenotype When accurately matched for age and obesity only LADA patients with antiGAD antibodies but not GADnegative/CD38positive patients have reduced in vivo βcell function in comparison to antibodynegative patients Transgenic mice overexpressing CD38 show enhanced glucoseinduced insulin release whereas conversely CD38 knockout mice display a severe impairment in βcell 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 glucoseinduced insulin secretion in human βcells 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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