Oral Presentation 6th Australian Health and Medical Research Congress 2012

Alteration of zinc and zinc transporter metabolism in a type 2 diabetic db/db mice model. (#140)

Mariea Bosco 1 2 3 , Daisy Mohanasundaram 2 , Chris Drogemuller 2 , Peter Zalewski 1 3 , Peter Coyle 4 , Allan Rofe 4 , Toby Coates 1 2 3
  1. Queen Elizabeth Hospital (Basil Hetzel Institute), Woodville West, SA, Australia
  2. Department of Nephrology, Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, SA, Australia
  3. University of Adelaide , Discipline of Medicine, Adelaide, South Australia, Australia
  4. Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia

Zinc is an important trace element shown to play an important structural and functional role in pancreas, being required by endocrine islet cells for insulin secretion and by exocrine acinar cells as pancreatic juice component1,2  . ZnT8 is a member of the SLC30A family of zinc transporters involved packaging and secretion insulin in response to glucose, suggesting a possible role in regulating glycemia. ZnT8 in studies identified polymorphisms in the ZnT8 gene conferring increased type 2 diabetes risk1,2  . Our study aims to investigate the zinc and zinc transporter regulation in a type 2 diabetic db/db mice model compared to the age matched control (C57BL6J) mice. Methods. Zinc was measured using flame atomic absorption spectrometry and Zinpyr-1 staining (labile pool) and Immunofluorescence was done using frozen sections of pancreas of control and diabetic mice and were stained using zinc transporter antibodies. Results. Db/db mice livers at 14 weeks showed significant reduction of zinc concentration compared to its age matched controls livers (49%, p<0.05, n=5). Db/db mice pancreas also showed significant reduction in zinc in the early diabetic mice (55%, p<0.05 n=6), diabetic (40%, p=0.0013, n=6) and chronic diabetic (26%, p=0.002,n=5) respectively compared to its aged matched controls. Zinc concentration in the plasma of the db/db mice were elevated compared to the controls. Pancreatic islets of 4, 10 and 18 weeks mice showed down regulation of efflux transporter ZnT8 and upregulation of influx transporter ZIP14 when counterstained with glucagon. Conclusion. The subcellular distribution of the zinc transporters ZnT8 and ZIP14 in 4, 10 and 18 week old mice db/db mice pancreas is altered during the progression of diabetes thereby affecting the zinc availability and regulation. Further experiments will be carried to investigate the regulation of these transporters using quantitative real time PCR.

  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.