ArticleThe Journal of biological chemistry2008
Chronic suppression of acetyl-CoA carboxylase 1 in beta-cells impairs insulin secretion via inhibition of glucose rather than lipid metabolism.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- An INS-1 832/13 𝛽-Cell Proteome Highlights the Rapid Regulation of Fatty Acid Biosynthesis in Glucose-Stimulated Insulin Secretion.Proteomics · 2025Article
- Evaluating the impact of lipids in isolated islet research.Frontiers in endocrinology · 2025Review
- Pharmacologic inhibition of lipogenesis for the treatment of NAFLD.Journal of hepatology · 2024Review
- Metabolic regulation of glucagon secretion.The Journal of endocrinology · 2023Article
- Maturation of beta cells: lessons from in vivo and in vitro models.Diabetologia · 2022Review
- Lipogenesis inhibitors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2022Review
- Acetyl-CoA-carboxylase 1 (ACC1) plays a critical role in glucagon secretion.Communications biology · 2022Article
- Prolyl-4-hydroxylase 3 maintains β cell glucose metabolism during fatty acid excess in mice.JCI insight · 2021Article
- Mechanisms controlling pancreatic islet cell function in insulin secretion.Nature reviews. Molecular cell biology · 2021Review
- Bilobalide Enhances AMPK Activity to Improve Liver Injury and Metabolic Disorders in STZ-Induced Diabetes in Immature Rats via Regulating HMGB1/TLR4/NF-BioMed research international · 2021Article
- Gender dependent differences in lipid metabolism in individuals with type 2 diabetes mellitus.Journal of diabetes and metabolic disorders · 2020Article
- Prognostic Value of the Overexpression of Fatty Acid Metabolism-Related Enzymes in Squamous Cell Carcinoma of the Head and Neck.International journal of molecular sciences · 2020Article
- Review
- Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice.International journal of molecular medicine · 2020Article
- Protein Kinase CK2-A Putative Target for the Therapy of Diabetes Mellitus?International journal of molecular sciences · 2019Review
- Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass.Diabetologia · 2019Article
- Article
- Article
- Metabolomics applied to the pancreatic islet.Archives of biochemistry and biophysics · 2016Review
- LKB1 couples glucose metabolism to insulin secretion in mice.Diabetologia · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Acetyl-CoA carboxylase 1 (ACC1) currently is being investigated as a target for treatment of obesity-associated dyslipidemia and insulin resistance. To investigate the effects of ACC1 inhibition on insulin secretion, three small interfering RNA (siRNA) duplexes targeting ACC1 (siACC1) were transfected into the INS-1-derived cell line, 832/13; the most efficacious duplex was also cloned into an adenovirus and used to transduce isolated rat islets. Delivery of the siACC1 duplexes decreased ACC1 mRNA by 60-80% in 832/13 cells and islets and enzyme activity by 46% compared with cells treated with a non-targeted siRNA. Delivery of siACC1 decreased glucose-stimulated insulin secretion (GSIS) by 70% in 832/13 cells and by 33% in islets. Surprisingly, siACC1 treatment decreased glucose oxidation by 49%, and the ATP:ADP ratio by 52%, accompanied by clear decreases in pyruvate cycling activity and tricarboxylic acid cycle intermediates. Exposure of siACC1-treated cells to the pyruvate cycling substrate dimethylmalate restored GSIS to normal without recovery of the depressed ATP:ADP ratio. In siACC1-treated cells, glucokinase protein levels were decreased by 25%, which correlated with a 36% decrease in glycogen synthesis and a 33% decrease in glycolytic flux. Furthermore, acute addition of the ACC1 inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) to beta-cells suppressed [(14)C]glucose incorporation into lipids but had no effect on GSIS, whereas chronic TOFA administration suppressed GSIS and glucose metabolism. In sum, chronic, but not acute, suppression of ACC1 activity impairs GSIS via inhibition of glucose rather than lipid metabolism. These findings raise concerns about the use of ACC inhibitors for diabetes therapy.
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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.