TY - JOUR
T1 - Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice
AU - Mensah-Brown, E. P.K.
AU - Al Rabesi, Z.
AU - Shahin, A.
AU - Al Shamsi, M.
AU - Arsenijevic, N.
AU - Hsu, D. K.
AU - Liu, F. T.
AU - Lukic, M. L.
N1 - Funding Information:
This work was supported by Sheikh Hamdan Award for Medical Sciences. We are thankful to Ms. Dawood for secretarial help.
PY - 2009/1
Y1 - 2009/1
N2 - Galectin 3 (Gal-3) is an antiapoptotic and a proinflammatory lectin. We hypothesized that the proinflammatory properties of Gal-3 may influence disease induction in the multiple low doses of streptozotocin model of diabetes. Diabetes was induced in C57BL/6 Gal-3+/+ and Gal-3-/- mice and disease monitored by blood glucose level, immuno-histology, insulin content of islets and expression of the proinflammatory cytokines, TNF-α, IFN-γ, IL-17, and iNOS in pancreatic lymph nodes. Gal-3+/+ mice developed delayed and sustained hyperglycemia, mononuclear cellular infiltration and reduced insulin content of islets accompanied with expression of proinflammatory cytokines. Gal-3-/- mice were relatively resistant to diabetogenesis as evaluated by glycemia, quantitative histology and insulin content. Further, we observed the weaker expression of IFN-γ and complete absence of TNF-α, and IL-17 in draining pancreatic lymph nodes. Macrophages, the first cells that infiltrate the islet in this model of diabetes, produce less TNF-α and NO in Gal-3-/- mice. Thus, Gal-3 is involved in immune mediated β cell damage and is required for diabetogenesis in this model of disease.
AB - Galectin 3 (Gal-3) is an antiapoptotic and a proinflammatory lectin. We hypothesized that the proinflammatory properties of Gal-3 may influence disease induction in the multiple low doses of streptozotocin model of diabetes. Diabetes was induced in C57BL/6 Gal-3+/+ and Gal-3-/- mice and disease monitored by blood glucose level, immuno-histology, insulin content of islets and expression of the proinflammatory cytokines, TNF-α, IFN-γ, IL-17, and iNOS in pancreatic lymph nodes. Gal-3+/+ mice developed delayed and sustained hyperglycemia, mononuclear cellular infiltration and reduced insulin content of islets accompanied with expression of proinflammatory cytokines. Gal-3-/- mice were relatively resistant to diabetogenesis as evaluated by glycemia, quantitative histology and insulin content. Further, we observed the weaker expression of IFN-γ and complete absence of TNF-α, and IL-17 in draining pancreatic lymph nodes. Macrophages, the first cells that infiltrate the islet in this model of diabetes, produce less TNF-α and NO in Gal-3-/- mice. Thus, Gal-3 is involved in immune mediated β cell damage and is required for diabetogenesis in this model of disease.
KW - Autoimmunity;
KW - Inducible nitric oxide synthase;
KW - Interferon-gamma;
KW - Interleukin-17
KW - Proinflammatory cytokines;
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U2 - 10.1016/j.clim.2008.08.024
DO - 10.1016/j.clim.2008.08.024
M3 - Article
C2 - 18845486
AN - SCOPUS:57149129697
SN - 1521-6616
VL - 130
SP - 83
EP - 88
JO - Clinical Immunology
JF - Clinical Immunology
IS - 1
ER -