ArticleThe Journal of clinical investigation1998
Chronic exposure to free fatty acid reduces pancreatic beta cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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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.
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Who cites it
61 citing papers in PubMed, 254 citations in OpenAlex.
- The antioxidant, N-acetyl-L-cysteine, affects beta cell oxidative stress, insulin secretion, and intracellular signaling pathways in MIN6 cells.Cell and tissue research · 2025Article
- Didymin protects pancreatic beta cells by enhancing mitochondrial function in high-fat diet-induced impaired glucose tolerance.Diabetology & metabolic syndrome · 2024Article
- Pathophysiological Mechanisms and Clinical Associations of Non-Alcoholic Fatty Pancreas Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.Diabetologia · 2023Article
- Very-Long-Chain Unsaturated Sphingolipids Mediate Oleate-Induced Rat β-Cell Proliferation.Diabetes · 2022Article
- Review
- Developmental programming: Prenatal testosterone excess disrupts pancreatic islet developmental trajectory in female sheep.Molecular and cellular endocrinology · 2020Article
- Effect of growth hormone on insulin signaling.Molecular and cellular endocrinology · 2020Review
- The making of insulin in health and disease.Diabetologia · 2020Review
- Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Reducing Glucokinase Activity to Enhance Insulin Secretion: A Counterintuitive Theory to Preserve Cellular Function and Glucose Homeostasis.Frontiers in endocrinology · 2020Article
- Effects of Dietary Fatty Acids in Pancreatic Beta Cell Metabolism, Implications in Homeostasis.Nutrients · 2018Review
- Cell culture models of fatty acid overload: Problems and solutions.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Review
- The dynamic plasticity of insulin production in β-cells.Molecular metabolism · 2017Review
- Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion.Scientific reports · 2017Article
- Article
- Article
- The role of ER stress in lipid metabolism and lipotoxicity.Journal of lipid research · 2016Review
- Inhibition of Monoacylglycerol Lipase Activity Decreases Glucose-Stimulated Insulin Secretion in INS-1 (832/13) Cells and Rat Islets.PloS one · 2016Article
- Functional Analysis of Novel Candidate Regulators of Insulin Secretion in the MIN6 Mouse Pancreatic β Cell Line.PloS one · 2016Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The pancreatic beta cell normally maintains a stable balance among insulin secretion, insulin production, and insulin degradation to keep optimal intracellular stores of the hormone. Elevated levels of FFA markedly enhance insulin secretion; however, the effects of FFA on insulin production and intracellular stores remain unclear. In this study, twofold elevation in total circulating FFA effected by infusion of lard oil and heparin into rats for 6 h under normoglycemic conditions resulted in a marked elevation of circulating insulin levels evident after 4 h, and a 30% decrease in pancreatic insulin content after a 6-h infusion in vivo. Adding 125 muM oleate to isolated rat pancreatic islets cultured with 5.6 mM glucose caused a 50% fall in their insulin content over 24 h, coupled with a marked enhancement of basal insulin secretion. Both effects of fatty acid were blocked by somatostatin. In contrast to the stimulatory effects of oleate on insulin secretion, glucose-induced proinsulin biosynthesis was inhibited by oleate up to 24 h, but was unaffected thereafter. This result was in spite of a two- to threefold oleate-induced increase in preproinsulin mRNA levels, underscoring the importance of translational regulation of proinsulin biosynthesis in maintaining beta cell insulin stores. Collectively, these results suggest that chronically elevated FFA contribute to beta cell dysfunction in the pathogenesis of NIDDM by significantly increasing the basal rate of insulin secretion. This increase in turn results in a decrease in the beta cell's intracellular stores that cannot be offset by commensurate FFA induction of proinsulin biosynthesis.
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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.