Israel Medical Association Journal

Background: Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.

Objectives: To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM[1] in a transfer model of NOD mice.

Methods: Our vaccination technique involved the insertion of CD44s[2] or CD44v[3] cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN[4] were implanted 20 days before and 3 days after cell transfer.

Results: In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.

Conclusions: These findings may open new opportunities for IDDM therapy in the future.

Background: Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM.

Objectives: To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice.

Methods: Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice.

Results: Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83±10.67 vs. 4.44±10.83 mmol/L, P<0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104±27 vs. 151±36 mol/L, P<0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups.

Conclusions: This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.

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IDDM= insulin-dependent diabetes mellitus

NOD= non-obese diabetic