Targeting interleukin-22 to the pancreas to treat type 2 diabetes mellitus — ASN Events
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  2. Poster Session Three
  3. Targeting interleukin-22 to the pancreas to treat type 2 diabetes mellitus

Targeting interleukin-22 to the pancreas to treat type 2 diabetes mellitus (#412)

Grace Yeung 1 2 , Sahar Keshvari 1 2 , Christian Fercher 3 , Ross Barnard 3 , John Prins 1 2 , Sumaira Hasnain 1 2 , Michael McGuckin 1 2
  1. Translational Research Institute, Parkinson, QLD, Australia
  2. Mater Research Institute, Brisbane, Queensland, Australia
  3. School of Chemistry and Molecular Biosciences , University of Queensland, Brisbane, Queensland, Australia

Background

Type 2 diabetes (T2D), coined the ‘silent pandemic’, is one of the most challenging global health problems facing the 21st century, affecting 1 in 11 adults worldwide. Current therapeutics fail to address pancreatic β-cell dysfunction and deterioration central to this disease. Previously, we demonstrated the seminal role of interleukin-22 (IL-22) in reversing pancreatic β-cell stress and restoring glycaemic control in murine models of diabetes (1). To further investigate the viability of IL-22 as a potential biologic for diabetes treatment, and to limit off-target effects, human IL-22 was fused to SCAB1, a pancreatic β-cell specific antibody. The resulting fusion protein (IL22-SCAB1) and its potential role in diabetes therapy is the subject of this study.

 Aims

Our objective is to elucidate whether IL22-SCAB1 is a functional biologic which can localise to the pancreas and activate downstream pathways of IL-22, thereby mediating anti-diabetic effects.

Methods

IL22-SCAB1 will be tested progressively. In preliminary stages, it will be trialled in vitro in MIN6.  Alterations in gene expression of β-cell stress markers will be measured. In vivo, IL22-SCAB1 will be administered to obese murine models of diabetes. Relevant diabetic parameters, including insulin-proinsulin ratio, body composition and glucose tolerance will be recorded.

Results

Early results demonstrate successful targeting and activation of IL-22 pathways, providing crucial preclinical information into the suitability of IL22-SCAB1 as a therapeutic candidate. IL22-SCAB1 may play a putative role in fat redistribution in obese non-diabetic mice.

Conclusion

IL22-SCAB1 may herald development of next-generation T2D therapeutic strategies, restoring pancreatic function in the diabetic patient.

  1. 1. Hasnain, S. Z. et al. Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress. Nature medicine 20, 1417-1426, doi:10.1038/nm.3705 (2014).
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