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Differential expression of glutamic acid decarboxylase in rat and human islets

Petersen, Jacob S. ; Russel, Steven ; Marshall, Michael O. ; Kofod, Hans ; Buschard, Karsten ; Cambon, Natalie ; Karlsen, Allan E. ; Boel, Esper ; Hagopian, William A. and Hejnæs, Kim R. , et al. (1993) In Diabetes 42(3). p.484-495
Abstract

The GABA synthesizing enzyme GAD is a prominent islet cell autoantigen in type I diabetes. The two forms of GAD (GAD64 and GAD67) are encoded by different genes in both rats and humans. By in situ hybridization analysis of rat and human pancreases, expression of both genes was detected in rat islets, whereas only GAD64 mRNA was detected in human islets, Immunocytochemical analysis of rat and human pancreatic sections or isolated islets with antibodies to GAD64 and GAD67 in combination with antibodies to insulin, glucagon, or SRIF confirmed that a GAD64 and GAD67 expression were β-cell specific in rat islets. In contrast, only GAD64 was detected in... (More)

The GABA synthesizing enzyme GAD is a prominent islet cell autoantigen in type I diabetes. The two forms of GAD (GAD64 and GAD67) are encoded by different genes in both rats and humans. By in situ hybridization analysis of rat and human pancreases, expression of both genes was detected in rat islets, whereas only GAD64 mRNA was detected in human islets, Immunocytochemical analysis of rat and human pancreatic sections or isolated islets with antibodies to GAD64 and GAD67 in combination with antibodies to insulin, glucagon, or SRIF confirmed that a GAD64 and GAD67 expression were β-cell specific in rat islets. In contrast, only GAD64 was detected in human islets and was, in addition to β-cells, also surprisingly localized to some α-cells, δ-cells, and PP-cells. In long-term (4 wk) monolayer cultures of newborn rat islet cells, GAD64 expression remained β-cell specific as observed in vivo, whereas GAD67 was localized not only to the β-cells but also in the α-cells and δ-cells. A small but distinct fraction of GAD positive cells in these monolayer cultures did not accumulate GABA immunoreactivity, which may indicate cellular heterogeneity with respect to GABA catabolism or GAD enzyme activity. In a rat insulinoma cell line (NHI-6F) producing both glucagon and insulin depending on the culture conditions, GAD64 expression was detected only in cultures in which the insulin producing phenotype dominated. In conclusion, these data demonstrate that the two GAD isoforms are differentially expressed in rat and human islets but also that the expression differs according to culture conditions. These findings emphasize the need to consider both the species and culture conditions of islets.

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publishing date
type
Contribution to journal
publication status
published
in
Diabetes
volume
42
issue
3
pages
484 - 495
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:0027461045
  • pmid:8432419
ISSN
0012-1797
DOI
10.2337/diab.42.3.484
language
English
LU publication?
no
id
daecae07-1750-4132-8163-b66800285fc5
date added to LUP
2019-09-11 09:25:34
date last changed
2024-03-13 08:00:48
@article{daecae07-1750-4132-8163-b66800285fc5,
  abstract     = {{<p>The GABA synthesizing enzyme GAD is a prominent islet cell autoantigen in type I diabetes. The two forms of GAD (GAD<sub>64</sub> and GAD<sub>67</sub>) are encoded by different genes in both rats and humans. By in situ hybridization analysis of rat and human pancreases, expression of both genes was detected in rat islets, whereas only GAD<sub>64</sub> mRNA was detected in human islets, Immunocytochemical analysis of rat and human pancreatic sections or isolated islets with antibodies to GAD<sub>64</sub> and GAD<sub>67</sub> in combination with antibodies to insulin, glucagon, or SRIF confirmed that a GAD<sub>64</sub> and GAD<sub>67</sub> expression were β-cell specific in rat islets. In contrast, only GAD<sub>64</sub> was detected in human islets and was, in addition to β-cells, also surprisingly localized to some α-cells, δ-cells, and PP-cells. In long-term (4 wk) monolayer cultures of newborn rat islet cells, GAD<sub>64</sub> expression remained β-cell specific as observed in vivo, whereas GAD<sub>67</sub> was localized not only to the β-cells but also in the α-cells and δ-cells. A small but distinct fraction of GAD positive cells in these monolayer cultures did not accumulate GABA immunoreactivity, which may indicate cellular heterogeneity with respect to GABA catabolism or GAD enzyme activity. In a rat insulinoma cell line (NHI-6F) producing both glucagon and insulin depending on the culture conditions, GAD<sub>64</sub> expression was detected only in cultures in which the insulin producing phenotype dominated. In conclusion, these data demonstrate that the two GAD isoforms are differentially expressed in rat and human islets but also that the expression differs according to culture conditions. These findings emphasize the need to consider both the species and culture conditions of islets.</p>}},
  author       = {{Petersen, Jacob S. and Russel, Steven and Marshall, Michael O. and Kofod, Hans and Buschard, Karsten and Cambon, Natalie and Karlsen, Allan E. and Boel, Esper and Hagopian, William A. and Hejnæs, Kim R. and Moody, Alistar and Dyrberg, Thomas and Lernmark, Åke and Madsen, Ole D. and Michelsen, Birgitte K.}},
  issn         = {{0012-1797}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{3}},
  pages        = {{484--495}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Differential expression of glutamic acid decarboxylase in rat and human islets}},
  url          = {{http://dx.doi.org/10.2337/diab.42.3.484}},
  doi          = {{10.2337/diab.42.3.484}},
  volume       = {{42}},
  year         = {{1993}},
}