Poster Presentation Australian Islet Study Group 2013

Islet specific reduction of zinc and alteration of zinc transporters in pancreatic islets of a type 2 diabetic db/db mice model (#16)

Mariea Bosco 1 2 3 4 , Daisy M Mohanasundaram 1 3 , Chris Drogemuller 1 3 , Peter Zalewski 2 , Toby P Coates 1 2 3 4
  1. Central and Northern Transplantation Services, Beverley, S.A, Australia
  2. Basil Hetzel Institute, The Queen Elizabeth Hospital, Adelaide, SA, Australia
  3. Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
  4. Robinson Institute, The University of Adelaide, Adelaide, SA, Australia

Zinc levels in the pancreatic islets is amongst the highest in the body being required by endocrine islet cells for insulin formation and by exocrine acinar cells as pancreas juice component and the reduction of zinc in the pancreas is linked with diabetes1 2  . ZnT8 is a member of the SLC30a8 family of zinc transporters involved in packaging and secretion of insulin in response to glucose also known as an efflux transporter, suggesting a possible role of zinc transporters in regulation of glycaemia1 2 . ZnT8 in studies identified polymorphisms in the ZnT8 gene conferring increased type 2 diabetes risk2 . Our study aims to investigate the zinc and zinc transporter regulation in a type 2 diabetic db/db mice model compared to age matched control (C57BL6J) mice. Methods. Zinc was measured using flame atomic absorption spectrometry and ZINPYR-1 staining (granular zinc) and Immunofluorescence was done using zinc transporter antibodies. Db/db mice pancreas showed significant reduction in zinc in early diabetic mice (p=0.008, n=6), diabetic (p=0.008, n=6) and chronic diabetic (p=0.07, n=6) respectively compared to age matched controls. ZINPYR-1 staining showed islet specific reduction of zinc in the pancreatic islets of db/db mice pancreatic islets at all age groups. No significant change was seen in the cytosolic zinc in the pancreas of the db/db mice. Pancreatic islets of 4,10 and 18 weeks mice showed downregulation of efflux transporter ZnT8 and Influx transporter ZIP4 and up regulation of ZIP14 protein expression when counterstained with glucagon. There was no significance change in the protein expression in ZIP5 protein in the pancreatic islets of db/db mice compared to the age matched controls, however significance increase in expression was seen in the acinar tissue. No change was seen in the gene level with these zinc transporters, suggesting that they are postranslationally regulated and altered in type 2 diabetes.

  1. Chistiakov DA, Voronova NV (2009).Zn(2+)-transporter-8: a dual role in diabetes. Biofactors 35(4):356-63.
  2. J Rungby (2010).Zinc, zinc transporters and diabetes. Diabetologia (53)1549-1551.