ArticleMolecular metabolism2015
PGC-1 coactivators in β-cells regulate lipid metabolism and are essential for insulin secretion coupled to fatty acids.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis.Marine drugs · 2021Trial
- β-Cell Dysfunction in COVID-19 and Post-COVID Syndrome: Molecular Mechanisms Linking Inflammation, Oxidative Stress, and Insulin Secretion.International journal of molecular sciences · 2026Review
- South African Herbal Teas and Diabetes-Mediated Mitochondrial Dysfunction: Emerging Evidence and Mechanistic Insights.Journal of food science · 2026Review
- Targeting PGC-1α by miRNA-374 Simultaneously Improve β-Cell Dysfunction and Suppress Hepatic Glucose Overproduction.Diabetes & metabolism journal · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Review
- β-Cell Mitochondrial Dysfunction: Underlying Mechanisms and Potential Therapeutic Strategies.Cells · 2025Review
- Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.Science (New York, N.Y.) · 2025Article
- Wet pulverization combined with temperature cycling strategy for extraction ofFood chemistry: X · 2025Article
- Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice.GeroScience · 2024Article
- Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis.Communications biology · 2024Article
- Subtherapeutic Kitasamycin Promoted Fat Accumulation in the Longissimus Dorsi Muscle in Growing-Finishing Pigs.Animals : an open access journal from MDPI · 2024Article
- CaFrontiers in endocrinology · 2024Review
- Downregulation of Kcnq1ot1 attenuates β-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis.Acta diabetologica · 2022Article
- Preparation of fatty acid solutions exerts significant impact on experimental outcomes in cell culture models of lipotoxicity.Biology methods & protocols · 2022Article
- Analysis of Gene Expression Profiles in the Liver of Rats With Intrauterine Growth Retardation.Frontiers in pediatrics · 2022Article
- The Tetracycline-Controlled Transactivator (Tet-On/Off) System in β-Cells Reduces Insulin Expression and Secretion in Mice.Diabetes · 2021Article
- Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer.Nature communications · 2021Article
- Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review.Antioxidants (Basel, Switzerland) · 2021Review
- The Role of Fatty Acid Signaling in Islet Beta-Cell Adaptation to Normal Pregnancy.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesPeroxisome proliferator-activated receptor γ coactivator 1 (PPARGCA1, PGC-1) transcriptional coactivators control gene programs important for nutrient metabolism. Islets of type 2 diabetic subjects have reduced PGC-1α expression and this is associated with decreased insulin secretion, yet little is known about why this occurs or what role it plays in the development of diabetes. Our goal was to delineate the role and importance of PGC-1 proteins to β-cell function and energy homeostasis.
methodsWe investigated how nutrient signals regulate coactivator expression in islets and the metabolic consequences of reduced PGC-1α and PGC-1β in primary and cultured β-cells. Mice with inducible β-cell specific double knockout of Pgc-1α/Pgc-1β (βPgc-1 KO) were created to determine the physiological impact of reduced Pgc1 expression on glucose homeostasis.
resultsPgc-1α and Pgc-1β expression was increased in primary mouse and human islets by acute glucose and palmitate exposure. Surprisingly, PGC-1 proteins were dispensable for the maintenance of mitochondrial mass, gene expression, and oxygen consumption in response to glucose in adult β-cells. However, islets and mice with an inducible, β-cell-specific PGC-1 knockout had decreased insulin secretion due in large part to loss of the potentiating effect of fatty acids. Consistent with an essential role for PGC-1 in lipid metabolism, β-cells with reduced PGC-1s accumulated acyl-glycerols and PGC-1s controlled expression of key enzymes in lipolysis and the glycerolipid/free fatty acid cycle.
conclusionsThese data highlight the importance of PGC-1s in coupling β-cell lipid metabolism to promote efficient insulin secretion.
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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 OpenQuestion graph.