ArticleDiabetes2013
Neprilysin deficiency protects against fat-induced insulin secretory dysfunction by maintaining calcium influx.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Impact of Sitagliptin on Neprilysin and Glycemic Control in Newly Diagnosed Type 2 Diabetes Patients.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Comparison of the therapeutic effects of sacubitril and valsartan combination versus metformin in experimentally induced polycystic ovary syndrome in rats.Iranian journal of basic medical sciences · 2025Article
- Gut-specific Neprilysin Deletion Protects Against Fat-induced Insulin Secretory Dysfunction in Male Mice.Endocrinology · 2024Article
- Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications.Frontiers in pharmacology · 2024Review
- Article
- Association between soluble neprilysin and diabetes: Findings from a prospective longitudinal study.Frontiers in endocrinology · 2023Article
- Neprilysin inhibition improves intravenous but not oral glucose-mediated insulin secretion via GLP-1R signaling in mice withAmerican journal of physiology. Endocrinology and metabolism · 2022Article
- Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling.Acta neuropathologica communications · 2022Article
- Insulinotropic Effects of Neprilysin and/or Angiotensin Receptor Inhibition in Mice.Frontiers in endocrinology · 2022Article
- Neprilysin Inhibition Increases Glucagon Levels in Humans and Mice With Potential Effects on Amino Acid Metabolism.Journal of the Endocrine Society · 2021Article
- Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Neprilysin inhibition: a new therapeutic option for type 2 diabetes?Diabetologia · 2019Review
- Increased urinary angiotensin converting enzyme 2 and neprilysin in patients with type 2 diabetes.American journal of physiology. Renal physiology · 2018Article
- Neprilysin Deficiency Is Associated With Expansion of Islet β-Cell Mass in High Fat-Fed Mice.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- Neprilysin inhibition in mouse islets enhances insulin secretion in a GLP-1 receptor dependent manner.Islets · 2018Article
- Improved glycaemia in high-fat-fed neprilysin-deficient mice is associated with reduced DPP-4 activity and increased active GLP-1 levels.Diabetologia · 2017Article
- Markers of Islet Endothelial Dysfunction Occur in Male B6.BKS(D)-Leprdb/J Mice and May Contribute to Reduced Insulin Release.Endocrinology · 2017Article
- Lipotoxicity in the pancreatic beta cell: not just survival and function, but proliferation as well?Current diabetes reports · 2014Review
- PLASMA NEPRILYSIN LEVELS IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME.Acta endocrinologica (Bucharest, Romania : 2005)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Neprilysin contributes to free fatty acid (FFA)-induced cellular dysfunction in nonislet tissues in type 2 diabetes. Here, we show for the first time that with prolonged FFA exposure, islet neprilysin is upregulated and this is associated with reduced insulin pre-mRNA and ATP levels, oxidative/nitrative stress, impaired potassium and calcium channel activities, and decreased glucose-stimulated insulin secretion (GSIS). Genetic ablation of neprilysin specifically protects against FFA-induced impairment of calcium influx and GSIS in vitro and in vivo but does not ameliorate other FFA-induced defects. Importantly, adenoviral overexpression of neprilysin in islets cultured without FFA reproduces the defects in both calcium influx and GSIS, suggesting that upregulation of neprilysin per se mediates insulin secretory dysfunction and that the mechanism for protection conferred by neprilysin deletion involves prevention of reduced calcium influx. Our findings highlight the critical nature of calcium signaling for normal insulin secretion and suggest that interventions to inhibit neprilysin may improve β-cell function in obese humans with type 2 diabetes.
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What OpenQuestion holds
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.