Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice.
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-alpha, IFN-gamma, 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-gamma and complete absence of TNF-alpha, and IL-17 in draining pancreatic lymph nodes. Macrophages, the first cells that infiltrate the islet in this model of diabetes, produce less TNF-alpha and NO in Gal-3(-/-) mice. Thus, Gal-3 is involved in immune mediated beta cell damage and is required for diabetogenesis in this model of disease.
Mensah-Brown
E P K
EP
Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
Al Rabesi
Z
Z
Shahin
A
A
Al Shamsi
M
M
Arsenijevic
N
N
Hsu
D K
DK
Liu
F-T
FT
Lukic
M L
ML
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004198:Disease Susceptibility; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology
D037502:Galectin 3; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D013311:Streptozocin