Cloning and characterization of cDNA encoding rat ADP-ribosyl cyclase / cyclic ADP-ribose hydrolase (homologue to human CD38) from islets of Langerhans

Aims/hypothesis. Autoantibodies against CD38 have been found in some patients with Type II (non-insulindependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i) overlaps with anti-GAD autoimmunity, (ii) identifies an insulin-deficient phenotype, (iii) is under the influence of genetic factors. Methods. We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects).Results. CD38-autoantibodies were found in 8.4% of Type II diabetic patients (p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD38ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti-CD38 positive had DQB1*02 compared with 38% of anti-CD38 negative (p=0.04).On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired (p=0.02) only in association with anti-GAD positivity (3.2±3.1 U/mol, mean ± SD) but not in anti-CD38 positive patients (5.6±2.9) as compared with patients free of autoimmunity (4.5±4.6, p=NS).In 44 Type II diabetic patients (22 negative and 22 positive for anti-CD38), no mutations were detected in any of the 8 exons, 5′ end of intron 1 or the 5′ and 3′ untranslated regions of the CD38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. Conclusion. Anti-CD38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence. [Diabetologia (2002[Diabetologia ( ) 45:1298[Diabetologia ( -1306

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“…pancreas [11,12,13]. In rat pancreatic islets, cADPR induces the release of calcium from microsomes [14].…”

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confidence: 99%

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

et al. 2002

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“…The expression of a CD38 homologue in various rat tissues has been detected including that of the spleen, liver, heart, thymus, thyroid gland, ileum, colon, cerebellum, salivary glands, jejunum and islets of Langerhans (6). CD38 has been shown to play an important regulatory role in insulin secretion via calcium mobilization from cADPR-sensitive stores (7).…”

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confidence: 99%

Purification and characterization of CD38/ADP‐ribosyl cyclase from rat lung

Khoo

Chang

1998

IUBMB Life

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SUMMARYPurification and characterization of CD38tADP-ribosyl cyctase in the rat lung tissue was performed with microsomes solubilized in Triton X-100 and the ADPribosyl cyclase was then purified using sequential column chromatography. Partially purified rat lung ADP-ribosyl cyclase was analyzed by immunoblotting using an antibody raised against a recombinant rat CD38 and showed the presence of monomer (42 kDa) and dimer (85 kDa) under non-reducing conditions but under reducing conditions, only the monomer was detected. Both the monomer and dimer could be eluted out in a stable manner from SDS-PAGE and the enzymatic activity was retained by the two different forms of CD38/ADPribosyl cyclase. Immunohistochemical staining showed the presence of CD38 on the bronchial epithelium and the alveoli.

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“…Although CD38 (NADase/ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) is expressed in pancreatic islets [1][2][3], the participation of cyclic ADP-ribose (cADPR) in the process of glucose-induced insulin release remains a matter of debate [4][5][6][7][8]. In a recent study [8], the cADPR content of rat pancreatic islets was found to much higher than that of liver, whole pancreas or tumoral islet cells, but failed to differ in islets incubated for 90 min in either the absence or presence of D-glucose (6.0 to 20.0 raM) and/or D-fructose (80.0 mM).…”

Section: Introductionmentioning

confidence: 99%

Effects of D‐glucose and starvation upon the cyclic ADP‐ribose content of rat pancreatic islets

Scruel¹,

Wada²,

Kontani³

et al. 1998

IUBMB Life

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SUMMARY: Rat pancreatic islets were found to display a much lower content of immunoreactive CD38 and a much lower ADP-ribosyl cyclase activity than rat spleen or brain. Cyclic ADP-ribose was also measured by a radioimmunological procedure in rat pancreatic islets. In fed rats, the cyclic ADP-ribose content appeared higher after isolation of the islets in the presence of 2.8 mM D-glucose rather than in the absence of the hexose, progressively increased during incubation of the islets for 5-60 min at 37~ but failed to be affected by the concentration of D-glucose (zero to 20.0 raM) in the incubation medium. In rats fasted for 24 hours, the cyclic ADP-ribose islet content also increased during incubation, but again failed to be affected by the concentration of D-glucose in the incubation medium. Although these findings indicate that the islet cyclic ADP-ribose content is influenced by nutritional and environmental factors, they do not support the view that the insulinotropic aciton of D-glucose involves major change in the islet cell content of the cyclic nucleotide.

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Cloning and characterization of cDNA encoding rat ADP-ribosyl cyclase / cyclic ADP-ribose hydrolase (homologue to human CD38) from islets of Langerhans

Cited by 107 publications

References 22 publications

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

Purification and characterization of CD38/ADP‐ribosyl cyclase from rat lung

Effects of D‐glucose and starvation upon the cyclic ADP‐ribose content of rat pancreatic islets

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