Skip to main content
Erschienen in: Inflammopharmacology 3/2019

12.02.2019 | Review Article

Zinc and its regulators in pancreas

verfasst von: Tianjiao Zhao, Qiongfang Huang, Yangni Su, Wuyi Sun, Qiong Huang, Wei Wei

Erschienen in: Inflammopharmacology | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Studies have demonstrated that susceptibility to type 2 diabetes (T2D) is influenced by common polymorphism in the zinc transporter 8 gene SLC30A8, providing novel insight into the role of zinc in diabetes. Intriguingly, zinc participates in every step of the process, including insulin synthesis, crystallization, storage, secretion and signaling. Zinc deficiency or overload is associated with various disorders, such as diabetes, cardiovascular disease and obesity. Zinc supplementation is considered as an effective means of treating or preventing T2D in people with certain SLC30A8 genotypes. Three important protein families—zinc transporters (ZnTs), zinc importers (ZiPs) and metallothionein (MT)—participate in maintaining zinc homeostasis. Here, we review research on the physiological characteristics of zinc and its role in the pancreas and homeostasis regulation mechanisms, along with the latest research on the structure and function of ZnT/ZiP and MT. In addition, we summarize the advancements in research on SLC30A8 gene polymorphism in search of a mechanism to explain the relationship between the R risk allele and zinc transporter activity.
Literatur
Zurück zum Zitat Bafaro E, Liu Y, Xu Y, Dempski RE (2017) The emerging role of zinc transporters in cellular homeostasis and cancer. Signal Transduct Target Ther 2:17029CrossRefPubMedPubMedCentral Bafaro E, Liu Y, Xu Y, Dempski RE (2017) The emerging role of zinc transporters in cellular homeostasis and cancer. Signal Transduct Target Ther 2:17029CrossRefPubMedPubMedCentral
Zurück zum Zitat Bellomo EA, Meur G, Rutter GA (2011) Glucose regulates free cytosolic Zn(2)(+) concentration, Slc39 (ZiP), and metallothionein gene expression in primary pancreatic islet beta-cells. J Biol Chem 286:25778–25789CrossRefPubMedPubMedCentral Bellomo EA, Meur G, Rutter GA (2011) Glucose regulates free cytosolic Zn(2)(+) concentration, Slc39 (ZiP), and metallothionein gene expression in primary pancreatic islet beta-cells. J Biol Chem 286:25778–25789CrossRefPubMedPubMedCentral
Zurück zum Zitat Boesgaard TW, Zilinskaite J, Vanttinen M, Laakso M, Jansson PA, Hammarstedt A, Smith U, Stefan N, Fritsche A, Haring H, Hribal M, Sesti G, Zobel DP, Pedersen O, Hansen T (2008) The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients–the EUGENE2 study. Diabetologia 51:816–820CrossRefPubMed Boesgaard TW, Zilinskaite J, Vanttinen M, Laakso M, Jansson PA, Hammarstedt A, Smith U, Stefan N, Fritsche A, Haring H, Hribal M, Sesti G, Zobel DP, Pedersen O, Hansen T (2008) The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients–the EUGENE2 study. Diabetologia 51:816–820CrossRefPubMed
Zurück zum Zitat Cai Y, Kirschke CP, Huang L (2018) SLC30A family expression in the pancreatic islets of humans and mice: cellular localization in the beta-cells. J Mol Histol 49:133–145CrossRefPubMed Cai Y, Kirschke CP, Huang L (2018) SLC30A family expression in the pancreatic islets of humans and mice: cellular localization in the beta-cells. J Mol Histol 49:133–145CrossRefPubMed
Zurück zum Zitat Carpene E, Andreani G, Isani G (2007) Metallothionein functions and structural characteristics. J Trace Elem Med Biol 21(Suppl 1):35–39CrossRefPubMed Carpene E, Andreani G, Isani G (2007) Metallothionein functions and structural characteristics. J Trace Elem Med Biol 21(Suppl 1):35–39CrossRefPubMed
Zurück zum Zitat Carvalho S, Molina-Lopez J, Parsons D, Corpe C, Maret W, Hogstrand C (2017) Differential cytolocation and functional assays of the two major human SLC30A8 (ZnT8) isoforms. J Trace Elem Med Biol 44:116–124CrossRefPubMed Carvalho S, Molina-Lopez J, Parsons D, Corpe C, Maret W, Hogstrand C (2017) Differential cytolocation and functional assays of the two major human SLC30A8 (ZnT8) isoforms. J Trace Elem Med Biol 44:116–124CrossRefPubMed
Zurück zum Zitat Cauchi S, Proenca C, Choquet H, Gaget S, DeGraeve F, Marre M, Balkau B, Tichet J, Meyre D, Vaxillaire M, Froguel P (2008) Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. Study. J Mol Med (Berl) 86:341–348CrossRef Cauchi S, Proenca C, Choquet H, Gaget S, DeGraeve F, Marre M, Balkau B, Tichet J, Meyre D, Vaxillaire M, Froguel P (2008) Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. Study. J Mol Med (Berl) 86:341–348CrossRef
Zurück zum Zitat Cauchi S, Del GS, Choquet H, D’Aleo V, Groves CJ, Lupi R, McCarthy MI, Froguel P, Marchetti P (2010) Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on isolated human pancreatic islets. Mol Genet Metab 100:77–82CrossRefPubMed Cauchi S, Del GS, Choquet H, D’Aleo V, Groves CJ, Lupi R, McCarthy MI, Froguel P, Marchetti P (2010) Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on isolated human pancreatic islets. Mol Genet Metab 100:77–82CrossRefPubMed
Zurück zum Zitat Chabosseau P, Rutter GA (2016) Zinc and diabetes. Arch Biochem Biophys 611:79–85CrossRef Chabosseau P, Rutter GA (2016) Zinc and diabetes. Arch Biochem Biophys 611:79–85CrossRef
Zurück zum Zitat Chabosseau P, Woodier J, Cheung R, Rutter GA (2018) Sensors for measuring subcellular zinc pools. Metallomics 10:229–239CrossRefPubMed Chabosseau P, Woodier J, Cheung R, Rutter GA (2018) Sensors for measuring subcellular zinc pools. Metallomics 10:229–239CrossRefPubMed
Zurück zum Zitat Chimienti F (2013) Zinc, pancreatic islet cell function and diabetes: new insights into an old story. Nutr Res Rev 26:1–11CrossRefPubMed Chimienti F (2013) Zinc, pancreatic islet cell function and diabetes: new insights into an old story. Nutr Res Rev 26:1–11CrossRefPubMed
Zurück zum Zitat Cipriano C, Malavolta M, Costarelli L, Giacconi R, Muti E, Gasparini N, Cardelli M, Monti D, Mariani E, Mocchegiani E (2006) Polymorphisms in MT1a gene coding region are associated with longevity in Italian central female population. Biogerontology 7:357–365CrossRefPubMed Cipriano C, Malavolta M, Costarelli L, Giacconi R, Muti E, Gasparini N, Cardelli M, Monti D, Mariani E, Mocchegiani E (2006) Polymorphisms in MT1a gene coding region are associated with longevity in Italian central female population. Biogerontology 7:357–365CrossRefPubMed
Zurück zum Zitat Cruz K, de Oliveira A, Morais J, Severo JS, Mendes P, de Sousa MS, de Sousa GS, Marreiro D (2018) Zinc and insulin resistance: biochemical and molecular aspects. Biol Trace Elem Res 186:407–412CrossRefPubMed Cruz K, de Oliveira A, Morais J, Severo JS, Mendes P, de Sousa MS, de Sousa GS, Marreiro D (2018) Zinc and insulin resistance: biochemical and molecular aspects. Biol Trace Elem Res 186:407–412CrossRefPubMed
Zurück zum Zitat Egefjord L, Petersen AB, Rungby J (2010) Zinc, alpha cells and glucagon secretion. Curr Diabetes Rev 6:52–57CrossRefPubMed Egefjord L, Petersen AB, Rungby J (2010) Zinc, alpha cells and glucagon secretion. Curr Diabetes Rev 6:52–57CrossRefPubMed
Zurück zum Zitat Fan M, Li W, Wang L, Gu S, Dong S, Chen M, Yin H, Zheng J, Wu X, Jin J, Jiang X, Cai J, Liu P, Zheng C (2016) Association of SLC30A8 gene polymorphism with type 2 diabetes, evidence from 46 studies: a meta-analysis. Endocrine 53:381–394CrossRefPubMed Fan M, Li W, Wang L, Gu S, Dong S, Chen M, Yin H, Zheng J, Wu X, Jin J, Jiang X, Cai J, Liu P, Zheng C (2016) Association of SLC30A8 gene polymorphism with type 2 diabetes, evidence from 46 studies: a meta-analysis. Endocrine 53:381–394CrossRefPubMed
Zurück zum Zitat Flannick J, Thorleifsson G, Beer NL, Jacobs SB, Grarup N, Burtt NP, Mahajan A, Fuchsberger C, Atzmon G, Benediktsson R, Blangero J, Bowden DW, Brandslund I, Brosnan J, Burslem F, Chambers J, Cho YS, Christensen C, Douglas DA, Duggirala R, Dymek Z, Farjoun Y, Fennell T, Fontanillas P, Forsen T, Gabriel S, Glaser B, Gudbjartsson DF, Hanis C, Hansen T, Hreidarsson AB, Hveem K, Ingelsson E, Isomaa B, Johansson S, Jorgensen T, Jorgensen ME, Kathiresan S, Kong A, Kooner J, Kravic J, Laakso M, Lee JY, Lind L, Lindgren CM, Linneberg A, Masson G, Meitinger T, Mohlke KL, Molven A, Morris AP, Potluri S, Rauramaa R, Ribel-Madsen R, Richard AM, Rolph T, Salomaa V, Segre AV, Skarstrand H, Steinthorsdottir V, Stringham HM, Sulem P, Tai ES, Teo YY, Teslovich T, Thorsteinsdottir U, Trimmer JK, Tuomi T, Tuomilehto J, Vaziri-Sani F, Voight BF, Wilson JG, Boehnke M, McCarthy MI, Njolstad PR, Pedersen O, Groop L, Cox DR, Stefansson K, Altshuler D (2014) Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat Genet 46:357–363CrossRefPubMedPubMedCentral Flannick J, Thorleifsson G, Beer NL, Jacobs SB, Grarup N, Burtt NP, Mahajan A, Fuchsberger C, Atzmon G, Benediktsson R, Blangero J, Bowden DW, Brandslund I, Brosnan J, Burslem F, Chambers J, Cho YS, Christensen C, Douglas DA, Duggirala R, Dymek Z, Farjoun Y, Fennell T, Fontanillas P, Forsen T, Gabriel S, Glaser B, Gudbjartsson DF, Hanis C, Hansen T, Hreidarsson AB, Hveem K, Ingelsson E, Isomaa B, Johansson S, Jorgensen T, Jorgensen ME, Kathiresan S, Kong A, Kooner J, Kravic J, Laakso M, Lee JY, Lind L, Lindgren CM, Linneberg A, Masson G, Meitinger T, Mohlke KL, Molven A, Morris AP, Potluri S, Rauramaa R, Ribel-Madsen R, Richard AM, Rolph T, Salomaa V, Segre AV, Skarstrand H, Steinthorsdottir V, Stringham HM, Sulem P, Tai ES, Teo YY, Teslovich T, Thorsteinsdottir U, Trimmer JK, Tuomi T, Tuomilehto J, Vaziri-Sani F, Voight BF, Wilson JG, Boehnke M, McCarthy MI, Njolstad PR, Pedersen O, Groop L, Cox DR, Stefansson K, Altshuler D (2014) Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat Genet 46:357–363CrossRefPubMedPubMedCentral
Zurück zum Zitat Foster M, Samman S (2010) Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus. Antioxid Redox Signal 13:1549–1573CrossRefPubMed Foster M, Samman S (2010) Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus. Antioxid Redox Signal 13:1549–1573CrossRefPubMed
Zurück zum Zitat Fu Y, Tian W, Pratt EB, Dirling LB, Shyng SL, Meshul CK, Cohen DM (2009) Down-regulation of ZnT8 expression in INS-1 rat pancreatic beta cells reduces insulin content and glucose-inducible insulin secretion. PLoS One 4:e5679CrossRefPubMedPubMedCentral Fu Y, Tian W, Pratt EB, Dirling LB, Shyng SL, Meshul CK, Cohen DM (2009) Down-regulation of ZnT8 expression in INS-1 rat pancreatic beta cells reduces insulin content and glucose-inducible insulin secretion. PLoS One 4:e5679CrossRefPubMedPubMedCentral
Zurück zum Zitat Gerber PA, Bellomo EA, Hodson DJ, Meur G, Solomou A, Mitchell RK, Hollinshead M, Chimienti F, Bosco D, Hughes SJ, Johnson PR, Rutter GA (2014) Hypoxia lowers SLC30A8/ZnT8 expression and free cytosolic Zn2+ in pancreatic beta cells. Diabetologia 57:1635–1644CrossRefPubMedPubMedCentral Gerber PA, Bellomo EA, Hodson DJ, Meur G, Solomou A, Mitchell RK, Hollinshead M, Chimienti F, Bosco D, Hughes SJ, Johnson PR, Rutter GA (2014) Hypoxia lowers SLC30A8/ZnT8 expression and free cytosolic Zn2+ in pancreatic beta cells. Diabetologia 57:1635–1644CrossRefPubMedPubMedCentral
Zurück zum Zitat Gunther V, Lindert U, Schaffner W (2012) The taste of heavy metals: gene regulation by MTF-1. Biochim Biophys Acta 1823:1416–1425CrossRefPubMed Gunther V, Lindert U, Schaffner W (2012) The taste of heavy metals: gene regulation by MTF-1. Biochim Biophys Acta 1823:1416–1425CrossRefPubMed
Zurück zum Zitat Gyulkhandanyan AV, Lee SC, Bikopoulos G, Dai F, Wheeler MB (2006) The Zn2+-transporting pathways in pancreatic beta-cells: a role for the L-type voltage-gated Ca2+ channel. J Biol Chem 281:9361–9372CrossRefPubMed Gyulkhandanyan AV, Lee SC, Bikopoulos G, Dai F, Wheeler MB (2006) The Zn2+-transporting pathways in pancreatic beta-cells: a role for the L-type voltage-gated Ca2+ channel. J Biol Chem 281:9361–9372CrossRefPubMed
Zurück zum Zitat Gyulkhandanyan AV, Lu H, Lee SC, Bhattacharjee A, Wijesekara N, Fox JE, MacDonald PE, Chimienti F, Dai FF, Wheeler MB (2008) Investigation of transport mechanisms and regulation of intracellular Zn2+ in pancreatic alpha-cells. J Biol Chem 283:10184–10197CrossRefPubMed Gyulkhandanyan AV, Lu H, Lee SC, Bhattacharjee A, Wijesekara N, Fox JE, MacDonald PE, Chimienti F, Dai FF, Wheeler MB (2008) Investigation of transport mechanisms and regulation of intracellular Zn2+ in pancreatic alpha-cells. J Biol Chem 283:10184–10197CrossRefPubMed
Zurück zum Zitat Hardy AB, Serino AS, Wijesekara N, Chimienti F, Wheeler MB (2011) Regulation of glucagon secretion by zinc: lessons from the beta cell-specific Znt8 knockout mouse model. Diabetes Obes Metab 13(Suppl 1):112–117CrossRefPubMed Hardy AB, Serino AS, Wijesekara N, Chimienti F, Wheeler MB (2011) Regulation of glucagon secretion by zinc: lessons from the beta cell-specific Znt8 knockout mouse model. Diabetes Obes Metab 13(Suppl 1):112–117CrossRefPubMed
Zurück zum Zitat Hardyman JE, Tyson J, Jackson KA, Aldridge C, Cockell SJ, Wakeling LA, Valentine RA, Ford D (2016) Zinc sensing by metal-responsive transcription factor 1 (MTF1) controls metallothionein and ZnT1 expression to buffer the sensitivity of the transcriptome response to zinc. Metallomics 8:337–343CrossRefPubMed Hardyman JE, Tyson J, Jackson KA, Aldridge C, Cockell SJ, Wakeling LA, Valentine RA, Ford D (2016) Zinc sensing by metal-responsive transcription factor 1 (MTF1) controls metallothionein and ZnT1 expression to buffer the sensitivity of the transcriptome response to zinc. Metallomics 8:337–343CrossRefPubMed
Zurück zum Zitat Haupt A, Guthoff M, Schafer SA, Kirchhoff K, Machicao F, Gallwitz B, Staiger H, Stefan N, Fritsche A, Haring HU (2009) The inhibitory effect of recent type 2 diabetes risk loci on insulin secretion is modulated by insulin sensitivity. J Clin Endocrinol Metab 94:1775–1780CrossRefPubMed Haupt A, Guthoff M, Schafer SA, Kirchhoff K, Machicao F, Gallwitz B, Staiger H, Stefan N, Fritsche A, Haring HU (2009) The inhibitory effect of recent type 2 diabetes risk loci on insulin secretion is modulated by insulin sensitivity. J Clin Endocrinol Metab 94:1775–1780CrossRefPubMed
Zurück zum Zitat Ishihara H, Maechler P, Gjinovci A, Herrera PL, Wollheim CB (2003) Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. Nat Cell Biol 5:330–335CrossRefPubMed Ishihara H, Maechler P, Gjinovci A, Herrera PL, Wollheim CB (2003) Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. Nat Cell Biol 5:330–335CrossRefPubMed
Zurück zum Zitat Kambe T, Hashimoto A, Fujimoto S (2014) Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Cell Mol Life Sci 71:3281–3295CrossRefPubMed Kambe T, Hashimoto A, Fujimoto S (2014) Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Cell Mol Life Sci 71:3281–3295CrossRefPubMed
Zurück zum Zitat Kambe T, Matsunaga M, Takeda TA (2017) Understanding the contribution of zinc transporters in the function of the early secretory pathway. Int J Mol Sci 18:2179CrossRefPubMedCentral Kambe T, Matsunaga M, Takeda TA (2017) Understanding the contribution of zinc transporters in the function of the early secretory pathway. Int J Mol Sci 18:2179CrossRefPubMedCentral
Zurück zum Zitat Kleiner S, Gomez D, Megra B, Na E, Bhavsar R, Cavino K, Xin Y, Rojas J, Dominguez-Gutierrez G, Zambrowicz B, Carrat G, Chabosseau P, Hu M, Murphy AJ, Yancopoulos GD, Rutter GA, Gromada J (2018) Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity. Proc Natl Acad Sci USA 115:E7642–E7649CrossRefPubMed Kleiner S, Gomez D, Megra B, Na E, Bhavsar R, Cavino K, Xin Y, Rojas J, Dominguez-Gutierrez G, Zambrowicz B, Carrat G, Chabosseau P, Hu M, Murphy AJ, Yancopoulos GD, Rutter GA, Gromada J (2018) Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity. Proc Natl Acad Sci USA 115:E7642–E7649CrossRefPubMed
Zurück zum Zitat Krezel A, Maret W (2017) The functions of metamorphic metallothioneins in zinc and copper metabolism. Int J Mol Sci 18:1237CrossRefPubMedCentral Krezel A, Maret W (2017) The functions of metamorphic metallothioneins in zinc and copper metabolism. Int J Mol Sci 18:1237CrossRefPubMedCentral
Zurück zum Zitat Kulkarni H, Mamtani M, Peralta JM, Diego V, Dyer TD, Goring H, Almasy L, Mahaney MC, Williams-Blangero S, Duggirala R, Curran JE, Blangero J (2016) Lack of association between SLC30A8 variants and type 2 diabetes in Mexican American families. J Diabetes Res 2016:6463214CrossRefPubMedPubMedCentral Kulkarni H, Mamtani M, Peralta JM, Diego V, Dyer TD, Goring H, Almasy L, Mahaney MC, Williams-Blangero S, Duggirala R, Curran JE, Blangero J (2016) Lack of association between SLC30A8 variants and type 2 diabetes in Mexican American families. J Diabetes Res 2016:6463214CrossRefPubMedPubMedCentral
Zurück zum Zitat Lemaire K, Ravier MA, Schraenen A, Creemers JW, Van de Plas R, Granvik M, Van Lommel L, Waelkens E, Chimienti F, Rutter GA, Gilon P, In’T VP, Schuit FC (2009) Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci USA 106:14872–14877CrossRefPubMed Lemaire K, Ravier MA, Schraenen A, Creemers JW, Van de Plas R, Granvik M, Van Lommel L, Waelkens E, Chimienti F, Rutter GA, Gilon P, In’T VP, Schuit FC (2009) Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci USA 106:14872–14877CrossRefPubMed
Zurück zum Zitat Lewis JP, Palmer ND, Hicks PJ, Sale MM, Langefeld CD, Freedman BI, Divers J, Bowden DW (2008) Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies. Diabetes 57:2220–2225CrossRefPubMedPubMedCentral Lewis JP, Palmer ND, Hicks PJ, Sale MM, Langefeld CD, Freedman BI, Divers J, Bowden DW (2008) Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies. Diabetes 57:2220–2225CrossRefPubMedPubMedCentral
Zurück zum Zitat Li L, Bai S, Sheline CT (2017) HZnT8 (Slc30a8) transgenic mice that overexpress the R325 W polymorph have reduced islet Zn2+ and proinsulin levels, increased glucose tolerance after a high-fat diet, and altered levels of pancreatic zinc binding proteins. Diabetes 66:551–559CrossRefPubMed Li L, Bai S, Sheline CT (2017) HZnT8 (Slc30a8) transgenic mice that overexpress the R325 W polymorph have reduced islet Zn2+ and proinsulin levels, increased glucose tolerance after a high-fat diet, and altered levels of pancreatic zinc binding proteins. Diabetes 66:551–559CrossRefPubMed
Zurück zum Zitat Maret W (2015) Analyzing free zinc(II) ion concentrations in cell biology with fluorescent chelating molecules. Metallomics 7:202–211CrossRefPubMed Maret W (2015) Analyzing free zinc(II) ion concentrations in cell biology with fluorescent chelating molecules. Metallomics 7:202–211CrossRefPubMed
Zurück zum Zitat Maruthur NM, Clark JM, Fu M, Linda KW, Shuldiner AR (2015) Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in old order amish. Diabetologia 58:295–303CrossRefPubMed Maruthur NM, Clark JM, Fu M, Linda KW, Shuldiner AR (2015) Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in old order amish. Diabetologia 58:295–303CrossRefPubMed
Zurück zum Zitat Merriman C, Huang Q, Rutter GA, Fu D (2016) Lipid-tuned zinc transport activity of human ZnT8 protein correlates with risk for type-2 diabetes. J Biol Chem 291:26950–26957CrossRefPubMedPubMedCentral Merriman C, Huang Q, Rutter GA, Fu D (2016) Lipid-tuned zinc transport activity of human ZnT8 protein correlates with risk for type-2 diabetes. J Biol Chem 291:26950–26957CrossRefPubMedPubMedCentral
Zurück zum Zitat Mitchell RK, Hu M, Chabosseau PL, Cane MC, Meur G, Bellomo EA, Carzaniga R, Collinson LM, Li WH, Hodson DJ, Rutter GA (2016) Molecular genetic regulation of Slc30a8/ZnT8 reveals a positive association with glucose tolerance. Mol Endocrinol 30:77–91CrossRefPubMed Mitchell RK, Hu M, Chabosseau PL, Cane MC, Meur G, Bellomo EA, Carzaniga R, Collinson LM, Li WH, Hodson DJ, Rutter GA (2016) Molecular genetic regulation of Slc30a8/ZnT8 reveals a positive association with glucose tolerance. Mol Endocrinol 30:77–91CrossRefPubMed
Zurück zum Zitat Ng MC, Park KS, Oh B, Tam CH, Cho YM, Shin HD, Lam VK, Ma RC, So WY, Cho YS, Kim HL, Lee HK, Chan JC, Cho NH (2008) Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 57:2226–2233CrossRefPubMedPubMedCentral Ng MC, Park KS, Oh B, Tam CH, Cho YM, Shin HD, Lam VK, Ma RC, So WY, Cho YS, Kim HL, Lee HK, Chan JC, Cho NH (2008) Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 57:2226–2233CrossRefPubMedPubMedCentral
Zurück zum Zitat Nicolson TJ, Bellomo EA, Wijesekara N, Loder MK, Baldwin JM, Gyulkhandanyan AV, Koshkin V, Tarasov AI, Carzaniga R, Kronenberger K, Taneja TK, Da SXG, Libert S, Froguel P, Scharfmann R, Stetsyuk V, Ravassard P, Parker H, Gribble FM, Reimann F, Sladek R, Hughes SJ, Johnson PR, Masseboeuf M, Burcelin R, Baldwin SA, Liu M, Lara-Lemus R, Arvan P, Schuit FC, Wheeler MB, Chimienti F, Rutter GA (2009) Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes 58:2070–2083CrossRefPubMedPubMedCentral Nicolson TJ, Bellomo EA, Wijesekara N, Loder MK, Baldwin JM, Gyulkhandanyan AV, Koshkin V, Tarasov AI, Carzaniga R, Kronenberger K, Taneja TK, Da SXG, Libert S, Froguel P, Scharfmann R, Stetsyuk V, Ravassard P, Parker H, Gribble FM, Reimann F, Sladek R, Hughes SJ, Johnson PR, Masseboeuf M, Burcelin R, Baldwin SA, Liu M, Lara-Lemus R, Arvan P, Schuit FC, Wheeler MB, Chimienti F, Rutter GA (2009) Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes 58:2070–2083CrossRefPubMedPubMedCentral
Zurück zum Zitat Norouzi S, Adulcikas J, Sohal SS, Myers S (2017) Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease. J Biomed Sci 24:87CrossRefPubMedPubMedCentral Norouzi S, Adulcikas J, Sohal SS, Myers S (2017) Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease. J Biomed Sci 24:87CrossRefPubMedPubMedCentral
Zurück zum Zitat Norouzi S, Adulcikas J, Sohal SS, Myers S (2018) Zinc stimulates glucose oxidation and glycemic control by modulating the insulin signaling pathway in human and mouse skeletal muscle cell lines. PLoS ONE 13:e191727CrossRef Norouzi S, Adulcikas J, Sohal SS, Myers S (2018) Zinc stimulates glucose oxidation and glycemic control by modulating the insulin signaling pathway in human and mouse skeletal muscle cell lines. PLoS ONE 13:e191727CrossRef
Zurück zum Zitat Omori S, Tanaka Y, Takahashi A, Hirose H, Kashiwagi A, Kaku K, Kawamori R, Nakamura Y, Maeda S (2008) Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes 57:791–795CrossRefPubMed Omori S, Tanaka Y, Takahashi A, Hirose H, Kashiwagi A, Kaku K, Kawamori R, Nakamura Y, Maeda S (2008) Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes 57:791–795CrossRefPubMed
Zurück zum Zitat Park L, Min D, Kim H, Chung HY, Lee CH, Park IS, Kim Y, Park Y (2011) Tat-enhanced delivery of metallothionein can partially prevent the development of diabetes. Free Radic Biol Med 51:1666–1674CrossRefPubMed Park L, Min D, Kim H, Chung HY, Lee CH, Park IS, Kim Y, Park Y (2011) Tat-enhanced delivery of metallothionein can partially prevent the development of diabetes. Free Radic Biol Med 51:1666–1674CrossRefPubMed
Zurück zum Zitat Pertusa J, Leon-Quinto T, Berna G, Tejedo JR, Hmadcha A, Bedoya FJ, Martin F, Soria B (2017) Zn2 + chelation by serum albumin improves hexameric Zn2 + -insulin dissociation into monomers after exocytosis. PLoS ONE 12:e187547CrossRef Pertusa J, Leon-Quinto T, Berna G, Tejedo JR, Hmadcha A, Bedoya FJ, Martin F, Soria B (2017) Zn2 + chelation by serum albumin improves hexameric Zn2 + -insulin dissociation into monomers after exocytosis. PLoS ONE 12:e187547CrossRef
Zurück zum Zitat Pound LD, Sarkar SA, Ustione A, Dadi PK, Shadoan MK, Lee CE, Walters JA, Shiota M, McGuinness OP, Jacobson DA, Piston DW, Hutton JC, Powell DR, O’Brien RM (2012) The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background. PLoS One 7:e40972CrossRefPubMedPubMedCentral Pound LD, Sarkar SA, Ustione A, Dadi PK, Shadoan MK, Lee CE, Walters JA, Shiota M, McGuinness OP, Jacobson DA, Piston DW, Hutton JC, Powell DR, O’Brien RM (2012) The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background. PLoS One 7:e40972CrossRefPubMedPubMedCentral
Zurück zum Zitat Prost AL, Bloc A, Hussy N, Derand R, Vivaudou M (2004) Zinc is both an intracellular and extracellular regulator of KATP channel function. J Physiol 559:157–167CrossRefPubMedPubMedCentral Prost AL, Bloc A, Hussy N, Derand R, Vivaudou M (2004) Zinc is both an intracellular and extracellular regulator of KATP channel function. J Physiol 559:157–167CrossRefPubMedPubMedCentral
Zurück zum Zitat Raudenska M, Gumulec J, Podlaha O, Sztalmachova M, Babula P, Eckschlager T, Adam V, Kizek R, Masarik M (2014) Metallothionein polymorphisms in pathological processes. Metallomics 6:55–68CrossRefPubMed Raudenska M, Gumulec J, Podlaha O, Sztalmachova M, Babula P, Eckschlager T, Adam V, Kizek R, Masarik M (2014) Metallothionein polymorphisms in pathological processes. Metallomics 6:55–68CrossRefPubMed
Zurück zum Zitat Ravier MA, Rutter GA (2005) Glucose or insulin, but not zinc ions, inhibit glucagon secretion from mouse pancreatic alpha-cells. Diabetes 54:1789–1797CrossRefPubMed Ravier MA, Rutter GA (2005) Glucose or insulin, but not zinc ions, inhibit glucagon secretion from mouse pancreatic alpha-cells. Diabetes 54:1789–1797CrossRefPubMed
Zurück zum Zitat Robertson RP, Zhou H, Slucca M (2011) A role for zinc in pancreatic islet beta-cell cross-talk with the alpha-cell during hypoglycaemia. Diabetes Obes Metab 13(Suppl 1):106–111CrossRefPubMed Robertson RP, Zhou H, Slucca M (2011) A role for zinc in pancreatic islet beta-cell cross-talk with the alpha-cell during hypoglycaemia. Diabetes Obes Metab 13(Suppl 1):106–111CrossRefPubMed
Zurück zum Zitat Rutter GA, Chabosseau P, Bellomo EA, Maret W, Mitchell RK, Hodson DJ, Solomou A, Hu M (2016) Intracellular zinc in insulin secretion and action: a determinant of diabetes risk? Proc Nutr Soc 75:61–72CrossRefPubMed Rutter GA, Chabosseau P, Bellomo EA, Maret W, Mitchell RK, Hodson DJ, Solomou A, Hu M (2016) Intracellular zinc in insulin secretion and action: a determinant of diabetes risk? Proc Nutr Soc 75:61–72CrossRefPubMed
Zurück zum Zitat Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson BK, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336CrossRefPubMed Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson BK, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336CrossRefPubMed
Zurück zum Zitat Schweiger M, Steffl M, Amselgruber WM (2016) Co-localization of the zinc transporter ZnT8 (slc30A8) with ghrelin and motilin in the gastrointestinal tract of pigs. Histol Histopathol 31:205–211PubMed Schweiger M, Steffl M, Amselgruber WM (2016) Co-localization of the zinc transporter ZnT8 (slc30A8) with ghrelin and motilin in the gastrointestinal tract of pigs. Histol Histopathol 31:205–211PubMed
Zurück zum Zitat Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345CrossRefPubMedPubMedCentral Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345CrossRefPubMedPubMedCentral
Zurück zum Zitat Shan Z, Bao W, Zhang Y, Rong Y, Wang X, Jin Y, Song Y, Yao P, Sun C, Hu FB, Liu L (2014) Interactions between zinc transporter-8 gene (SLC30A8) and plasma zinc concentrations for impaired glucose regulation and type 2 diabetes. Diabetes 63:1796–1803CrossRefPubMed Shan Z, Bao W, Zhang Y, Rong Y, Wang X, Jin Y, Song Y, Yao P, Sun C, Hu FB, Liu L (2014) Interactions between zinc transporter-8 gene (SLC30A8) and plasma zinc concentrations for impaired glucose regulation and type 2 diabetes. Diabetes 63:1796–1803CrossRefPubMed
Zurück zum Zitat Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885CrossRefPubMed Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885CrossRefPubMed
Zurück zum Zitat Slepchenko KG, Daniels NA, Guo A, Li YV (2015) Autocrine effect of Zn(2)(+) on the glucose-stimulated insulin secretion. Endocrine 50:110–122CrossRefPubMed Slepchenko KG, Daniels NA, Guo A, Li YV (2015) Autocrine effect of Zn(2)(+) on the glucose-stimulated insulin secretion. Endocrine 50:110–122CrossRefPubMed
Zurück zum Zitat Slucca M, Harmon JS, Oseid EA, Bryan J, Robertson RP (2010) ATP-sensitive K+ channel mediates the zinc switch-off signal for glucagon response during glucose deprivation. Diabetes 59:128–134CrossRefPubMed Slucca M, Harmon JS, Oseid EA, Bryan J, Robertson RP (2010) ATP-sensitive K+ channel mediates the zinc switch-off signal for glucagon response during glucose deprivation. Diabetes 59:128–134CrossRefPubMed
Zurück zum Zitat Smidt K, Larsen A, Bronden A, Sorensen KS, Nielsen JV, Praetorius J, Martensen PM, Rungby J (2016) The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression. Biometals 29:287–298CrossRefPubMed Smidt K, Larsen A, Bronden A, Sorensen KS, Nielsen JV, Praetorius J, Martensen PM, Rungby J (2016) The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression. Biometals 29:287–298CrossRefPubMed
Zurück zum Zitat Solomou A, Meur G, Bellomo E, Hodson DJ, Tomas A, Li SM, Philippe E, Herrera PL, Magnan C, Rutter GA (2015) The zinc transporter Slc30a8/ZnT8 is required in a subpopulation of pancreatic alpha-cells for hypoglycemia-induced glucagon secretion. J Biol Chem 290:21432–21442CrossRefPubMedPubMedCentral Solomou A, Meur G, Bellomo E, Hodson DJ, Tomas A, Li SM, Philippe E, Herrera PL, Magnan C, Rutter GA (2015) The zinc transporter Slc30a8/ZnT8 is required in a subpopulation of pancreatic alpha-cells for hypoglycemia-induced glucagon secretion. J Biol Chem 290:21432–21442CrossRefPubMedPubMedCentral
Zurück zum Zitat Sun W, Yang J, Wang W, Hou J, Cheng Y, Fu Y, Xu Z, Cai L (2018) The beneficial effects of Zn on Akt-mediated insulin and cell survival signaling pathways in diabetes. J Trace Elem Med Biol 46:117–127CrossRefPubMed Sun W, Yang J, Wang W, Hou J, Cheng Y, Fu Y, Xu Z, Cai L (2018) The beneficial effects of Zn on Akt-mediated insulin and cell survival signaling pathways in diabetes. J Trace Elem Med Biol 46:117–127CrossRefPubMed
Zurück zum Zitat Syring KE, Boortz KA, Oeser JK, Ustione A, Platt KA, Shadoan MK, McGuinness OP, Piston DW, Powell DR, O’Brien RM (2016) Combined deletion of slc30a7 and slc30a8 unmasks a critical role for ZnT8 in glucose-stimulated insulin secretion. Endocrinology 157:4534–4541CrossRefPubMedPubMedCentral Syring KE, Boortz KA, Oeser JK, Ustione A, Platt KA, Shadoan MK, McGuinness OP, Piston DW, Powell DR, O’Brien RM (2016) Combined deletion of slc30a7 and slc30a8 unmasks a critical role for ZnT8 in glucose-stimulated insulin secretion. Endocrinology 157:4534–4541CrossRefPubMedPubMedCentral
Zurück zum Zitat Tamaki M, Fujitani Y, Hara A, Uchida T, Tamura Y, Takeno K, Kawaguchi M, Watanabe T, Ogihara T, Fukunaka A, Shimizu T, Mita T, Kanazawa A, Imaizumi MO, Abe T, Kiyonari H, Hojyo S, Fukada T, Kawauchi T, Nagamatsu S, Hirano T, Kawamori R, Watada H (2013) The diabetes-susceptible gene SLC30A8/ZnT8 regulates hepatic insulin clearance. J Clin Investig 123:4513–4524CrossRefPubMed Tamaki M, Fujitani Y, Hara A, Uchida T, Tamura Y, Takeno K, Kawaguchi M, Watanabe T, Ogihara T, Fukunaka A, Shimizu T, Mita T, Kanazawa A, Imaizumi MO, Abe T, Kiyonari H, Hojyo S, Fukada T, Kawauchi T, Nagamatsu S, Hirano T, Kawamori R, Watada H (2013) The diabetes-susceptible gene SLC30A8/ZnT8 regulates hepatic insulin clearance. J Clin Investig 123:4513–4524CrossRefPubMed
Zurück zum Zitat Votsi C, Toufexis C, Michailidou K, Antoniades A, Skordis N, Karaolis M, Pattichis CS, Christodoulou K (2017) Type 2 diabetes susceptibility in the Greek-cypriot population: replication of associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 polymorphisms. Genes (Basel) 8:16CrossRef Votsi C, Toufexis C, Michailidou K, Antoniades A, Skordis N, Karaolis M, Pattichis CS, Christodoulou K (2017) Type 2 diabetes susceptibility in the Greek-cypriot population: replication of associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 polymorphisms. Genes (Basel) 8:16CrossRef
Zurück zum Zitat Weijers RN (2010) Three-dimensional structure of beta-cell-specific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W. Diabetol Metab Syndr 2:33CrossRefPubMedPubMedCentral Weijers RN (2010) Three-dimensional structure of beta-cell-specific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W. Diabetol Metab Syndr 2:33CrossRefPubMedPubMedCentral
Zurück zum Zitat Wijesekara N, Dai FF, Hardy AB, Giglou PR, Bhattacharjee A, Koshkin V, Chimienti F, Gaisano HY, Rutter GA, Wheeler MB (2010) Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia 53:1656–1668CrossRefPubMedPubMedCentral Wijesekara N, Dai FF, Hardy AB, Giglou PR, Bhattacharjee A, Koshkin V, Chimienti F, Gaisano HY, Rutter GA, Wheeler MB (2010) Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia 53:1656–1668CrossRefPubMedPubMedCentral
Zurück zum Zitat Wong WP, Allen NB, Meyers MS, Link EO, Zhang X, MacRenaris KW, El MM (2017) Exploring the association between demographics, SLC30A8 genotype, and human islet content of zinc, cadmium, copper, iron, manganese and nickel. Sci Rep 7:473CrossRefPubMedPubMedCentral Wong WP, Allen NB, Meyers MS, Link EO, Zhang X, MacRenaris KW, El MM (2017) Exploring the association between demographics, SLC30A8 genotype, and human islet content of zinc, cadmium, copper, iron, manganese and nickel. Sci Rep 7:473CrossRefPubMedPubMedCentral
Zurück zum Zitat Wu W, Wang X, Zhang W, Reed W, Samet JM, Whang YE, Ghio AJ (2003) Zinc-induced PTEN protein degradation through the proteasome pathway in human airway epithelial cells. J Biol Chem 278:28258–28263CrossRefPubMed Wu W, Wang X, Zhang W, Reed W, Samet JM, Whang YE, Ghio AJ (2003) Zinc-induced PTEN protein degradation through the proteasome pathway in human airway epithelial cells. J Biol Chem 278:28258–28263CrossRefPubMed
Zurück zum Zitat Wu Y, Li H, Loos RJ, Yu Z, Ye X, Chen L, Pan A, Hu FB, Lin X (2008) Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 57:2834–2842CrossRefPubMedPubMedCentral Wu Y, Li H, Loos RJ, Yu Z, Ye X, Chen L, Pan A, Hu FB, Lin X (2008) Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 57:2834–2842CrossRefPubMedPubMedCentral
Zurück zum Zitat Yu T, Jiang Z, Liu L, Fan Z (2018) Decrease of gamma-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia. Exp Ther Med 15:2507–2511PubMed Yu T, Jiang Z, Liu L, Fan Z (2018) Decrease of gamma-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia. Exp Ther Med 15:2507–2511PubMed
Zurück zum Zitat Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney AS, McCarthy MI, Hattersley AT (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341CrossRefPubMedPubMedCentral Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney AS, McCarthy MI, Hattersley AT (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341CrossRefPubMedPubMedCentral
Zurück zum Zitat Zhou H, Zhang T, Harmon JS, Bryan J, Robertson RP (2007) Zinc, not insulin, regulates the rat alpha-cell response to hypoglycemia in vivo. Diabetes 56:1107–1112CrossRefPubMed Zhou H, Zhang T, Harmon JS, Bryan J, Robertson RP (2007) Zinc, not insulin, regulates the rat alpha-cell response to hypoglycemia in vivo. Diabetes 56:1107–1112CrossRefPubMed
Metadaten
Titel
Zinc and its regulators in pancreas
verfasst von
Tianjiao Zhao
Qiongfang Huang
Yangni Su
Wuyi Sun
Qiong Huang
Wei Wei
Publikationsdatum
12.02.2019
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 3/2019
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-019-00573-w

Weitere Artikel der Ausgabe 3/2019

Inflammopharmacology 3/2019 Zur Ausgabe