ArticleDiabetologia2025
Diet-enhanced LRG1 expression promotes insulin hypersecretion and ER stress in pancreatic beta cells.
Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Integrative multi-omics analysis of DNA methylome and transcriptome in a tyrosine kinase inhibitor LPM4870108-induced rat model of obesity.International journal of obesity (2005) · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Intermittent fasting ameliorates MAFLD by downregulating Lrg1: insights from bulk RNA sequencing and functional verification.Frontiers in endocrinology · 2026Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
aims/hypothesisUpregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.
methodsHuman serum samples were obtained from individuals (both male and female) undergoing plastic surgery. Male C57BL/6 wild-type and Lrg1 whole-body knockout (Lrg1
resultsWe observed a significant positive association between human serum LRG1 levels and both age and BMI, with elevated levels observed in individuals with vs without type 2 diabetes. In mice fed a high-fat diet, LRG1 upregulation in serum was associated with hyperinsulinaemia. Lrg1 knockout protected mice from diet-induced islet hyperplasia and the loss of beta cell mass. Furthermore, neutralising LRG1 activity prevented the onset of diet-induced hyperinsulinaemia and preserved glucose tolerance. Mechanistically, LRG1 induces inositol triphosphate (IP CONCLUSIONS/
interpretationIn summary, this study identifies LRG1 as a significant contributor to hyperinsulinaemia and beta cell dysfunction. Targeting LRG1 activity emerges as a promising therapeutic approach for addressing diet-induced beta cell dysfunction and managing type 2 diabetes.
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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 Socratic graph.