R. Vasan1, F. Kuehn1, J. Ramirez1, F. Adiliaghdam1, E. Liu1, Y. Liu1, M. Farber1, R. Pepen1, C. Freguia2, M. Kaleko2, R. A. Hodin1 1Massachusetts General Hospital,General Surgery,Boston, MA, USA 2Synthetic Biologics,Rockville, MD, USA
Introduction:
Intestinal alkaline phosphatase (IAP) maintains intestinal barrier integrity, prevents translocation of bacterially-derived products into the bloodstream, and diminishes low-grade systemic inflammation thought to contribute to diabetes mellitus pathogenesis. We have recently described the expression of IAP within pancreatic islets themselves. We aimed to determine resilience of IAP-KO animals to β-cell damage.
Methods:
A 5-day low-dose 40mg/kg/day, intraperitoneal streptozotocin (STZ) injection protocol was utilized as a model of T1DM β-cell damage. 12-week-old C57BL/6J Wild Type and IAP-KO mice received i.p. STZ or vehicle (4 groups, n=5). Study duration was 5 weeks. Measurements included periodic blood glucose, weekly food intake and weights, and daily water intake. Serum insulin and c-peptide were measured at sacrifice. Pancreatic islets were harvested for histology and insulin staining.
Results:
Blood glucose was significantly increased at 5 weeks in IAP-KO mice injected with STZ compared to their WT counterparts (554.2+/-37.2 vs. 296.4+/-11.6 mg/dL, p<0.01), as was food (47.8 vs. 23.5 g/week, p<0.05) and water intake (14.2 vs. 5.8ml/day, p<0.01). Serum insulin and c-peptide levels were markedly reduced – (21.1 vs. 75.4 µU/ml, p<0.01) and (0.43 vs. 1.22 ng/ml, p<0.01) respectively.
Conclusion:
IAP-KO mice in this study were more susceptible to STZ-induced β-cell damage and developed significantly worse diabetes compared to their WT counterparts. These results suggest that in addition to its well-recognized role in promoting gut barrier function, IAP may also serve a protective function within the pancreatic islets.