Istituto di Fisiologia Clinica     
Pupilli C., Giannini S., Marchetti P., Lupi R., Antonelli A., Malavasi F., Takasawa S., Okamoto H., Ferrannini E. Autoantibodies to CD38 (ADP-Ribosyl Cyclase/Cyclic ADP-Ribose Hydrolase) in Caucasian Patients With Diabetes Effects on Insulin Release From Human Islets. In: Diabetes, vol. 48 pp. 2309 - 2315. the American Diabetes Association, 1999.
The type II transmembrane glycoprotein CD38 (ADPribosyl cyclase/cyclic ADP-ribose hydrolase) has been proposed as a mediator of insulin secretion from pancreatic b-cells and as a candidate for autoimmune reactions in type 2 diabetes. We evaluated the presence of anti-CD38 autoantibodies in Caucasian patients with diabetes and investigated the effect of these antibodies on insulin secretion from isolated human pancreatic islets. The presence of anti-CD38 autoantibodies was evaluated by using Western blot analysis in 236 patients with type 2 diabetes (mean age 63 years), in 160 patients with type 1 diabetes (mean age 38 years), and in 159 nondiabetic subjects. Anti-CD38 autoantibody titers at least 3 SD above the mean value of the control group were found in 9.7% of type 2 diabetic patients and in 13.1% of type 1 diabetic patients (x2 = 15.9, P = 0.0003 vs. 1.3% of control subjects). No significant differences were observed in sex distribution, current age, age at diabetes onset, BMI, fasting serum glucose, or glycemic control between anti-CD38+ and anti-CD38- diabetic patients in either the type 2 or type 1 diabetic groups. The effect of 23 anti-CD38- and 13 anti-CD38+ sera on insulin secretion at low (3.3 mmol/l) or high (16.7 mmol/l) medium glucose concentrations was evaluated in isolated human pancreatic islets. Data are medians (interquartile range). The anti-CD38+ s e r a potentiated insulin release both at low [95 (64) vs. 23 (12) μU/ml of control incubations, respectively, P < 0.0001] and high [271 (336) vs. a control of 55 (37) μU/ml, respectively, P = 0.001] medium glucose concentrations, whereas the anti-CD38- sera did not. Furthermore, in the pooled data from all 36 tested sera, insulin levels in the islet incubation medium were directly related to the anti-CD38 antibody titer. We conclude that autoantibodies to CD38 are associated with both type 1 and type 2 diabetes in Caucasian subjects. These autoantibodies exert a stimulatory effect on insulin secretion by cultured human islets. The role of this autoimmune reaction in the pathogenesis of diabetes remains to be elucidated.
URL: http://diabetes.diabetesjournals.org/cgi/reprint/48/12/2309?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=pupilli&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
Subject Insulin

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