title: Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells.
abstract: BACKGROUND
  Zinc is essential for the activities of pancreatic β-cells, especially insulin storage and secretion. Insulin secretion leads to co-release of zinc which contributes to the paracrine communication in the pancreatic islets. Zinc-transporting proteins (zinc-regulated transporter, iron-regulated transporter-like proteins [ZIPs] and zinc transporters [ZnTs]) and metal-buffering proteins (metallothioneins, MTs) tightly regulate intracellular zinc homeostasis. The present study investigated how modulation of cellular zinc availability affects β-cell function using INS-1E cells.
  
  
  RESULTS
  Using INS-1E cells, we found that zinc supplementation and zinc chelation had significant effects on insulin content and insulin secretion. Supplemental zinc within the physiological concentration range induced insulin secretion. Insulin content was reduced by zinc chelation with N,N,N',N-tektrakis(2-pyridylmethyl)-ethylenediamine. The changes in intracellular insulin content following exposure to various concentrations of zinc were reflected by changes in the expression patterns of MT-1A, ZnT-8, ZnT-5, and ZnT-3. Furthermore, high zinc concentrations induced cell necrosis while zinc chelation induced apoptosis. Finally, cell proliferation was sensitive to changes in zinc the concentration.
  
  
  CONCLUSIONS
  These results indicate that the β-cell-like function and survival of INS-1E cells are dependent on the surrounding zinc concentrations. Our results suggest that regulation of zinc homeostasis could represent a pharmacological target.
authors: Department of Biomedicine, Centre of Pharmacology and Pharmacotherapy, Health, Aarhus University, Wilhelm Meyers Allé 4, Bld 1240, Aarhus, 8000, Denmark. sbn@farm.au.dk.
authors: Sanne Bjørn
authors: SB
authors: Nygaard
authors: Agnete
authors: A
authors: Larsen
authors: Astrid
authors: A
authors: Knuhtsen
authors: Jørgen
authors: J
authors: Rungby
authors: Kamille
authors: K
authors: Smidt
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D009336:Necrosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; D002614:Chelating Agents; D018076:DNA, Complementary; D005029:Ethylenediamines; D007328:Insulin; C491055:Mt2A protein, rat; D012333:RNA, Messenger; C542071:Slc30a8 protein, rat; D000075703:Zinc Transporter 8; C503697:zinc transporter 3, rat; C000591231:zinc transporter 5, rat; D008668:Metallothionein; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine