ArticleDiabetes2014
ADCY5 couples glucose to insulin secretion in human islets.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 153 citations in OpenAlex.
- Article
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- Bridging the variant-to-function gap in type 2 diabetes: advances and challenges.Diabetologia · 2026Review
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- DEC1 regulates human β cell functional maturation and circadian rhythm.Cell reports · 2025Article
- Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon.Cell genomics · 2025Article
- Integration of epigenomic and genomic data to predict residual feed intake and the feed conversion ratio in dairy sheep via machine learning algorithms.BMC genomics · 2025Article
- Heterogeneous effects of genetic variants and traits associated with fasting insulin on cardiometabolic outcomes.Nature communications · 2025Article
- Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.Cell metabolism · 2024Article
- Identification of genetic risk variants for Type-2 Diabetes mellitus in Pakistani Pashtun population: A case-control association study.Pakistan journal of medical sciences · 2024Article
- Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy.Metabolites · 2024Review
- Inquiry of the Metabolic Traits in Relationship with Daily Magnesium Intake: Focus on Type 2 Diabetic Population.Clinics and practice · 2024Review
- Paracrine Signaling by Pancreatic Islet Cilia.Current opinion in endocrine and metabolic research · 2024Article
- The MODY-associatedeLife · 2024Article
- Keeping pace: the primary cilium as the conducting baton of the islet.Diabetologia · 2024Review
- Multiple genetic variants at the SLC30A8 locus affect local super-enhancer activity and influence pancreatic β-cell survival and function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Functional interrogation of twenty type 2 diabetes-associated genes using isogenic human embryonic stem cell-derived β-like cells.Cell metabolism · 2023Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 5 countries.
Funding
Abstract
Single nucleotide polymorphisms (SNPs) within the ADCY5 gene, encoding adenylate cyclase 5, are associated with elevated fasting glucose and increased type 2 diabetes (T2D) risk. Despite this, the mechanisms underlying the effects of these polymorphic variants at the level of pancreatic β-cells remain unclear. Here, we show firstly that ADCY5 mRNA expression in islets is lowered by the possession of risk alleles at rs11708067. Next, we demonstrate that ADCY5 is indispensable for coupling glucose, but not GLP-1, to insulin secretion in human islets. Assessed by in situ imaging of recombinant probes, ADCY5 silencing impaired glucose-induced cAMP increases and blocked glucose metabolism toward ATP at concentrations of the sugar >8 mmol/L. However, calcium transient generation and functional connectivity between individual human β-cells were sharply inhibited at all glucose concentrations tested, implying additional, metabolism-independent roles for ADCY5. In contrast, calcium rises were unaffected in ADCY5-depleted islets exposed to GLP-1. Alterations in β-cell ADCY5 expression and impaired glucose signaling thus provide a likely route through which ADCY5 gene polymorphisms influence fasting glucose levels and T2D risk, while exerting more minor effects on incretin action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.