P-236

Role of zinc and zinc transporters in diabetic pancreatic islets

D. Mohanasundaram¹, C. Drogemullar¹, M. Bosco², C. Lang³, P. Zalewski³, T. Coates^3
1 Royal Adelaide Hospital, CNARTS, Adelaide, Australia; ² Basil Hetzel institute, TQEH, Adelaide, Australia; ³ Department of Medicine, University of Adelaide, Adelaide, Australia

Background: Zinc is a trace element necessary forcell survival that participates in the structure and function of many proteins.Zinc is vital for fundamental cellular mechanisms including DNA replication,metabolic enzyme activity and cellular protection against apo ptosisand oxidative stress. Zinchomeostasis is crucial for normal beta cell function and is regulated by z inctransporter proteins . Zinc transporter ZnT8 is specific to islets and essential for the formation of insulin crystals in thebeta cells, contributing to the packaging efficiency of stored insulin. Recentgenome wide association studies demonstrated single nucleotide polymorphisms ofZnT8 gene in human type2 diabetes and also identified as an auto antigen in human type1 diabetes.

Aim: The aim of the present study wasto investigate the alteration in zinc and regulation of zinc transporters intype 2 diabetic islets.

Methods: Zuckerdiabetic rat islets were stained for zinquin to see the level of zinc in the pancreaticislets using frozen sections. The florescence intensity was measured in normalobese and diabetic Zucker islets. Frozen sections of Human type 2 diabeticislets were stained for ZnT8 and Zip14 expression by immuno-histochemisty. Realtime PCR using Taqman primers and probe sets were carried out on normal andtype 2 diabetic pancreatic tissues for the expression of different zinctransporters.

Results: The resultsshowed that there was a significant reduction in zinc level in Zucker diabeticislets. The Immunostaining on human type 2 diabetic islets showed partial tocomplete down regulation of ZnT8 where as the gene expression at the mRNA levelshowed significant down regulation of Zip1, Zip5, Zip7and Zip 14. The differential regulation of zinc transporter at the molecular level using morehuman samples will give clear understanding on the role of these transportersin the aetiology of diabetes.

P-236

Role of zinc and zinc transporters in diabetic pancreatic islets

D. Mohanasundaram¹, C. Drogemullar¹, M. Bosco², C. Lang³, P. Zalewski³, T. Coates^3
1 Royal Adelaide Hospital, CNARTS, Adelaide, Australia; ² Basil Hetzel institute, TQEH, Adelaide, Australia; ³ Department of Medicine, University of Adelaide, Adelaide, Australia

Background: Zinc is a trace element necessary forcell survival that participates in the structure and function of many proteins.Zinc is vital for fundamental cellular mechanisms including DNA replication,metabolic enzyme activity and cellular protection against apo ptosisand oxidative stress. Zinchomeostasis is crucial for normal beta cell function and is regulated by z inctransporter proteins . Zinc transporter ZnT8 is specific to islets and essential for the formation of insulin crystals in thebeta cells, contributing to the packaging efficiency of stored insulin. Recentgenome wide association studies demonstrated single nucleotide polymorphisms ofZnT8 gene in human type2 diabetes and also identified as an auto antigen in human type1 diabetes.

Aim: The aim of the present study wasto investigate the alteration in zinc and regulation of zinc transporters intype 2 diabetic islets.

Methods: Zuckerdiabetic rat islets were stained for zinquin to see the level of zinc in the pancreaticislets using frozen sections. The florescence intensity was measured in normalobese and diabetic Zucker islets. Frozen sections of Human type 2 diabeticislets were stained for ZnT8 and Zip14 expression by immuno-histochemisty. Realtime PCR using Taqman primers and probe sets were carried out on normal andtype 2 diabetic pancreatic tissues for the expression of different zinctransporters.

Results: The resultsshowed that there was a significant reduction in zinc level in Zucker diabeticislets. The Immunostaining on human type 2 diabetic islets showed partial tocomplete down regulation of ZnT8 where as the gene expression at the mRNA levelshowed significant down regulation of Zip1, Zip5, Zip7and Zip 14. The differential regulation of zinc transporter at the molecular level using morehuman samples will give clear understanding on the role of these transportersin the aetiology of diabetes.