ArticleDiabetologia2022
Glucose-mediated insulin secretion is improved in FHL2-deficient mice and elevated FHL2 expression in humans is associated with type 2 diabetes.
Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 24 citations in OpenAlex.
- FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasis.Genes & diseases · 2026Review
- ATF6 ameliorates renal warm ischemia-reperfusion injury through FHL2-mediated NF-κB signaling pathway.iScience · 2026Article
- Imeglimin, unlike metformin, does not perturb differentiation of human induced pluripotent stem cells towards pancreatic β-like cells and rather enhances gain in β cell identity gene sets.Journal of diabetes investigation · 2025Article
- Article
- Effects of the FHL2 gene on the development of subcutaneous and intramuscular adipocytes in goats.BMC genomics · 2024Article
- Adipocyte-specific FAK deletion promotes pancreatic β-cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus.Clinical and translational medicine · 2024Article
- Biomarkers of aging.Science China. Life sciences · 2023Review
- FHL2 Genetic Polymorphisms and Pro-Diabetogenic Lipid Profile in the Multiethnic HELIUS Cohort.International journal of molecular sciences · 2023Article
- Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe general population is ageing, involving an enhanced incidence of chronic diseases such as type 2 diabetes. With ageing, DNA methylation of FHL2 increases, as well as expression of the four and a half LIM domains 2 (FHL2) protein in human pancreatic islets. We hypothesised that FHL2 is actively involved in glucose metabolism.
methodsPublicly available microarray datasets from human pancreatic islets were analysed for FHL2 expression. In FHL2-deficient mice, we studied glucose clearance and insulin secretion. Gene expression analysis and glucose-stimulated insulin secretion (GSIS) were determined in isolated murine FHL2-deficient islets to evaluate insulin-secretory capacity. Moreover, knockdown and overexpression of FHL2 were accomplished in MIN6 cells to delineate the underlying mechanism of FHL2 function.
resultsTranscriptomics of human pancreatic islets revealed that individuals with elevated levels of HbA CONCLUSIONS/
interpretationOur data demonstrate that FHL2 deficiency improves insulin secretion from beta cells and improves glucose tolerance in mice. Given that FHL2 expression in humans increases with age and that high expression levels of FHL2 are associated with beta cell dysfunction, we propose that enhanced FHL2 expression in elderly individuals contributes to glucose intolerance and the development of type 2 diabetes. DATA AVAILABILITY: The human islet microarray datasets used are publicly available and can be found on https://www.ncbi.nlm.nih.gov/geo/ .
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