Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

Norouzi, Shaghayegh; Adulcikas, John; Sohal, Sukhwinder Singh; Myers, Stephen

doi:10.1186/s12929-017-0394-0

Cited by 50 publications

(45 citation statements)

References 84 publications

(90 reference statements)

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“…The Slc39a family was named ZIP (Zrt-, Irt-related protein), after the first two known members Irt1 of Arabidopsis thaliana and Zrt1 of Saccharomyces cerevisiae . So far, the exact structure of mammalian ZIP proteins has not been established, but 14 members of human and mouse ZIP isoforms and their genes have been isolated and characterized [16,17,35]. ZIP family members mediate Zn 2+ influx from the extracellular place into cells, or from the intracellular Zn 2+ store into the cytoplasm, thereby increasing cytoplasmic Zn 2+ concentrations.…”

Section: Zn2+ Homeostasis In Megakaryocytes and Plateletsmentioning

confidence: 99%

“…Several isoforms of ZIP were predominantly expressed, including ZIP1, ZIP4, ZIP6, ZIP7, ZIP9 and ZIP10, while other ZIP isoforms showed limited mRNA expression, and ZIP2 was not detected [26]. Studies in mouse models showed the relevance of ZIP transporters in the regulation of systemic or cellular Zn 2+ homeostasis [16,17,36], but the function of these transporters have been investigated neither in MKs nor in platelets. The members of Slc30a gene family, also called ZnT, are selective Zn 2+ transporters located in the cell surface and on the membrane of intracellular organelles.…”

Section: Zn2+ Homeostasis In Megakaryocytes and Plateletsmentioning

confidence: 99%

“…Cellular Zn 2+ uptake can increase the activity of several enzymes, such as mitogen-activated protein kinases (MAPKs), caspases and metalloproteinases (MMPs), [1,9,10,11,12]. Many of secretory cells, such as pancreatic β-cells, neutrophils and platelets, can uptake, store and release a significant amount of Zn 2+ , regulating diverse Zn 2+ -dependent intracellular and extracellular pathways [3,8,13,14,15,16,17,18,19]. Zn 2+ is also responsible for maintaining the protein structure in zinc-finger transcription factors and LIM domain proteins, thus Zn 2+ can be coordinated by oxygen, sulfur and nitrogen atoms of the polypeptide chain [20].…”

Section: Introductionmentioning

confidence: 99%

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Zinc Homeostasis in Platelet-Related Diseases

Mammadova‐Bach

Braun

2019

IJMS

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Zn2+ deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn2+-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn2+ deficiency, clinical symptoms are associated with impaired wound healing, alopecia, diarrhea, poor growth, dysfunction of the immune and nervous system with congenital abnormalities and bleeding disorders. Poor nutritional Zn2+ status in patients with metastatic squamous cell carcinoma or with advanced non-Hodgkin lymphoma, was accompanied by cutaneous bleeding and platelet dysfunction. Forcing Zn2+ uptake in the gut using different nutritional supplementation of Zn2+ could ameliorate many of these pathological symptoms in humans. Feeding adult rodents with a low Zn2+ diet caused poor platelet aggregation and increased bleeding tendency, thereby attracting great scientific interest in investigating the role of Zn2+ in hemostasis. Storage protein metallothionein maintains or releases Zn2+ in the cytoplasm, and the dynamic change of this cytoplasmic Zn2+ pool is regulated by the redox status of the cell. An increase of labile Zn2+ pool can be toxic for the cells, and therefore cytoplasmic Zn2+ levels are tightly regulated by several Zn2+ transporters located on the cell surface and also on the intracellular membrane of Zn2+ storage organelles, such as secretory vesicles, endoplasmic reticulum or Golgi apparatus. Although Zn2+ is a critical cofactor for more than 2000 transcription factors and 300 enzymes, regulating cell differentiation, proliferation, and basic metabolic functions of the cells, the molecular mechanisms of Zn2+ transport and the physiological role of Zn2+ store in megakaryocyte and platelet function remain elusive. In this review, we summarize the contribution of extracellular or intracellular Zn2+ to megakaryocyte and platelet function and discuss the consequences of dysregulated Zn2+ homeostasis in platelet-related diseases by focusing on thrombosis, ischemic stroke and storage pool diseases.

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Section: Zn2+ Homeostasis In Megakaryocytes and Plateletsmentioning

confidence: 99%

Section: Zn2+ Homeostasis In Megakaryocytes and Plateletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Zinc Homeostasis in Platelet-Related Diseases

Mammadova‐Bach

Braun

2019

IJMS

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“…Rice bran is also rich in potassium, and diets low in potassium have been associated with an increased risk of diabetes in epidemiological studies [ 46 ]. Magnesium, zinc, and calcium supplementation has been shown to improve glycemic control, and cellular pathways involving these minerals have been linked to glucose and insulin homeostasis [ 47 , 48 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Co-Ingestion of Rice Bran Soymilk or Plain Soymilk with White Bread: Effects on the Glycemic and Insulinemic Response

et al. 2018

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The regular consumption of soy products is associated with inverse incidence of type 2 diabetes, and there has been an increasing interest in the glycemia reducing potential of rice bran and its components. In this study, we investigated whether consuming soymilk with the addition of rice bran (fiber) can reduce the glycemic response of a carbohydrate meal. Seventeen healthy Asian men (BMI: 18.5–29 kg/m2) participated in this randomized crossover trial. On four occasions, they consumed white bread (two times) and white bread with two different soymilks differing in protein and rice bran content. Blood samples were taken to measure glucose and insulin response over a period of 3 hours. Taking the glycemic index (GI) value of white bread as a reference value of 100, the GI of white bread when co-ingested with rice bran soymilk (RBS) was 83.1 (±7.7) and sugar-free soymilk (SFS) was 77.5 (±10.1), both were lower than white bread (p < 0.05). The insulin response of both soymilk treatments was similar to white bread (p > 0.05). The glucose/insulin ratio of RBS and SFS were respectively 43.1 (±6.1) and 60.0 (±17.0) and were lower (p < 0.05) than white bread (123.5 ± 21.1) during the first 30 min. In conclusion, co-ingestion of low amounts of soy protein with a carbohydrate meal stimulated early-phase insulin secretion and thereby increased blood glucose clearance effectiveness. Furthermore, rice bran-fortified soymilk reduced the glycemic response similarly to soymilk with a greater dose of soy protein. Rice bran and its components offer therapeutic potential for glycemic and insulinemic control.

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“…Type 2 diabetes is a progressive and chronic metabolic disease and it is characterized by peripheral insulin resistance and pancreatic beta β cell dysfunction with a growing interest in the role of zinc signaling in this disease [173,189]. GWAS of the past decade have identified variants in the human SLC30A8 gene as affecting the risk of Type 2 Diabetes [189]. Genome-wide association studies demonstrate an association of the above mentioned rs13266634 SNP of ZnT8 with decreased insulin release and T2DM susceptibility [43].…”

Section: Genetic Polymorphisms Involved In Zinc Status and Non Communmentioning

confidence: 99%

Genetic Polymorphisms and Zinc Status: Implications for Supplementation in Metabolic Diseases

Virgili

Ambra

McCormack

et al. 2019

CPD

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Background: Zinc is an essential component for all living organisms, representing the second most abundant trace element, after iron. This element is widely distributed in the tissues of human body where it is involved in the normal growth, reproduction and several biological functions including immunity, energy metabolism and antioxidant processes. Because of its essential role, zinc levels in human body must remain constant, independently of dietary intake fluctuations. The homeostasis of zinc is a well-regulated cellular process and has been reported to be chiefly mediated by the expression and activity of zinc-binding proteins such as metallothioneins and zinc transporters. Genes encoding for these proteins are subjected to genetic variants. Methods: We performed a multi-database electronic search to provide an overview on the relationship between specific polymorphisms (SNP) of genes encoding for metallothioneins and zinc transporters and their relationship with zinc status, immune function and some non-communicable diseases. Results: A number of SNP are implicated in a range of metabolic disease. Some SNP may affect the impact of zinc supplementation on immune function, diabetes, obesity. Conclusion: New studies are needed to clarify the interaction between individual genetic profile and zinc status. Moreover, there is a need to a better interaction between the scientific bodies and health professionals to allow better dietary and behavioural recommendations to promote human health, with particular concern to elderly people.

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Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

Cited by 50 publications

References 84 publications

Zinc Homeostasis in Platelet-Related Diseases

Zinc Homeostasis in Platelet-Related Diseases

Co-Ingestion of Rice Bran Soymilk or Plain Soymilk with White Bread: Effects on the Glycemic and Insulinemic Response

Genetic Polymorphisms and Zinc Status: Implications for Supplementation in Metabolic Diseases

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