ArticleJCI insight2021
Pancreatic β cell-selective zinc transporter 8 insufficiency accelerates diabetes associated with islet amyloidosis.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction.Diabetes & metabolism journal · 2026Article
- Glycine receptor activation promotes pancreatic islet cell proliferation via the PI3K/mTORC1/p70S6K pathway.JCI insight · 2025Article
- Flavones in pomelo peel resist fibril formation of human islet amyloid polypeptide.Chinese herbal medicines · 2025Article
- Severe Dietary Zinc Deficiency Does Not Significantly Alter Energy Balance in Adult Mice.Journal of nutrition and metabolism · 2025Article
- PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.Frontiers in pharmacology · 2024Review
- Impact of anFrontiers in endocrinology · 2023Article
- Validating expression of beta cell maturation-associated genes in human pancreas development.Frontiers in cell and developmental biology · 2023Article
- Review
- Latent autoimmune diabetes in adults: a focus on β-cell protection and therapy.Frontiers in endocrinology · 2022Review
- Adaptive Changes in Glucose Homeostasis and Islet Function During Pregnancy: A Targeted Metabolomics Study in Mice.Frontiers in endocrinology · 2022Article
- Multiomics Integrated Analysis IdentifiesJournal of diabetes research · 2022Article
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GWAS have shown that the common R325W variant of SLC30A8 (ZnT8) increases the risk of type 2 diabetes (T2D). However, ZnT8 haploinsufficiency is protective against T2D in humans, counterintuitive to earlier work in humans and mouse models. Therefore, whether decreasing ZnT8 activity is beneficial or detrimental to β cell function, especially under conditions of metabolic stress, remains unknown. In order to examine whether the existence of human islet amyloid polypeptide (hIAPP), a coresident of the insulin granule, affects the role of ZnT8 in regulating β cell function, hIAPP-expressing transgenics were generated with reduced ZnT8 (ZnT8B+/- hIAPP) or null ZnT8 (ZnT8B-/- hIAPP) expression specifically in β cells. We showed that ZnT8B-/- hIAPP mice on a high-fat diet had intensified amyloid deposition and further impaired glucose tolerance and insulin secretion compared with control, ZnT8B-/-, and hIAPP mice. This can in part be attributed to impaired glucose sensing and islet cell synchronicity. Importantly, ZnT8B+/- hIAPP mice were also glucose intolerant and had reduced insulin secretion and increased amyloid aggregation compared with controls. These data suggest that loss of or reduced ZnT8 activity in β cells heightened the toxicity induced by hIAPP, leading to impaired β cell function and glucose homeostasis associated with metabolic stress.
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