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. 1993 Jun;92(3):391–396. doi: 10.1111/j.1365-2249.1993.tb03410.x

Expression of glutamic acid decarboxylase (GAD) in the alpha, beta and delta cells of normal and diabetic pancreas: implications for the pathogenesis of type I diabetes.

M Vives-Pi 1, N Somoza 1, F Vargas 1, P Armengol 1, Y Sarri 1, J Y Wu 1, R Pujol-Borrell 1
PMCID: PMC1554778  PMID: 8513574

Abstract

One of the paradoxes of insulin-dependent diabetes mellitus is that the destruction of the pancreatic islets' endocrine cells is restricted to the insulin-producing beta cells, whereas the main autoantibodies, islet cell antibodies (ICA), are directed against all endocrine islet cells. GAD has recently been proposed as the main target of the humoral and cellular autoimmune attack to the islets, and since in rat pancreas this enzyme was expressed only in the beta cells, this provided an explanation for the cell specificity of the destructive process. The finding of GAD-positive cells in the islets of two diabetic patients, one of whom had completely lost the beta cells, led us to study in detail the distribution of GAD in normal human islet cells using a panel of GAD antisera and the double indirect immunofluorescence technique on cryostat sections, monolayer cultures and cytosmears. The results showed that GAD is present not only in the cytoplasm of beta cells but also in 69% of the alpha and 27% of the delta cells. GAD was not present, however, on the surface of the islet cells. These results suggest that the cellular distribution of GAD can not by itself explain the selectivity of beta cell destruction in insulin-dependent diabetes mellitus.

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Selected References

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  1. Atkinson M. A., Kaufman D. L., Campbell L., Gibbs K. A., Shah S. C., Bu D. F., Erlander M. G., Tobin A. J., Maclaren N. K. Response of peripheral-blood mononuclear cells to glutamate decarboxylase in insulin-dependent diabetes. Lancet. 1992 Feb 22;339(8791):458–459. doi: 10.1016/0140-6736(92)91061-c. [DOI] [PubMed] [Google Scholar]
  2. Baekkeskov S., Aanstoot H. J., Christgau S., Reetz A., Solimena M., Cascalho M., Folli F., Richter-Olesen H., De Camilli P., Camilli P. D. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature. 1990 Sep 13;347(6289):151–156. doi: 10.1038/347151a0. [DOI] [PubMed] [Google Scholar]
  3. Bottazzo G. F., Florin-Christensen A., Doniach D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet. 1974 Nov 30;2(7892):1279–1283. doi: 10.1016/s0140-6736(74)90140-8. [DOI] [PubMed] [Google Scholar]
  4. Chang Y. C., Gottlieb D. I. Characterization of the proteins purified with monoclonal antibodies to glutamic acid decarboxylase. J Neurosci. 1988 Jun;8(6):2123–2130. doi: 10.1523/JNEUROSCI.08-06-02123.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Erlander M. G., Tillakaratne N. J., Feldblum S., Patel N., Tobin A. J. Two genes encode distinct glutamate decarboxylases. Neuron. 1991 Jul;7(1):91–100. doi: 10.1016/0896-6273(91)90077-d. [DOI] [PubMed] [Google Scholar]
  6. Erlander M. G., Tobin A. J. The structural and functional heterogeneity of glutamic acid decarboxylase: a review. Neurochem Res. 1991 Mar;16(3):215–226. doi: 10.1007/BF00966084. [DOI] [PubMed] [Google Scholar]
  7. Genovese S., Bonifacio E., McNally J. M., Dean B. M., Wagner R., Bosi E., Gale E. A., Bottazzo G. F. Distinct cytoplasmic islet cell antibodies with different risks for type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1992 Apr;35(4):385–388. doi: 10.1007/BF00401207. [DOI] [PubMed] [Google Scholar]
  8. Giorda R., Peakman M., Tan K. C., Vergani D., Trucco M. Glutamic acid decarboxylase expression in islets and brain. Lancet. 1991 Dec 7;338(8780):1469–1470. doi: 10.1016/0140-6736(91)92781-v. [DOI] [PubMed] [Google Scholar]
  9. Karlsen A. E., Hagopian W. A., Grubin C. E., Dube S., Disteche C. M., Adler D. A., Bärmeier H., Mathewes S., Grant F. J., Foster D. Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8337–8341. doi: 10.1073/pnas.88.19.8337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaufman D. L., Erlander M. G., Clare-Salzler M., Atkinson M. A., Maclaren N. K., Tobin A. J. Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest. 1992 Jan;89(1):283–292. doi: 10.1172/JCI115573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Latif Z. A., Noel J., Alejandro R. A simple method of staining fresh and cultured islets. Transplantation. 1988 Apr;45(4):827–830. [PubMed] [Google Scholar]
  12. Srikanta S., Telen M., Posillico J. T., Dolinar R., Krisch K., Haynes B. F., Eisenbarth G. S. Monoclonal antibodies to a human islet cell surface glycoprotein: 4F2 and LC7-2. Endocrinology. 1987 Jun;120(6):2240–2244. doi: 10.1210/endo-120-6-2240. [DOI] [PubMed] [Google Scholar]
  13. Vives M., Sarri Y., Conget I., Somoza N., Alcade L., Armengol P., Fernández J., Lorenzo C., Martí M., Soldevila G. Human islet function after automatic isolation and bovine serum albumin gradient purification. Transplantation. 1992 Jan;53(1):243–245. [PubMed] [Google Scholar]
  14. Wu J. Y., Denner L. A., Wei S. C., Lin C. T., Song G. X., Xu Y. F., Liu J. W., Lin H. S. Production and characterization of polyclonal and monoclonal antibodies to rat brain L-glutamate decarboxylase. Brain Res. 1986 May 14;373(1-2):1–14. doi: 10.1016/0006-8993(86)90309-4. [DOI] [PubMed] [Google Scholar]

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