ArticleAmerican journal of physiology. Endocrinology and metabolism2009
Whole body overexpression of PGC-1alpha has opposite effects on hepatic and muscle insulin sensitivity.
Article in American journal of physiology. Endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- Are Mitochondria a Potential Target for Treating β-Thalassemia?Journal of clinical medicine · 2025Review
- PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.Science advances · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Specificity Proteins (SP) and Krüppel-like Factors (KLF) in Liver Physiology and Pathology.International journal of molecular sciences · 2023Review
- Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review.Neural regeneration research · 2021Review
- Hepatic transcriptional responses to fasting and feeding.Genes & development · 2021Review
- Dose- and time-dependent alterations in lipid metabolism after pharmacological PGC-1α activation in L6 myotubes.Journal of cellular physiology · 2019Article
- PGC-1α activation: a therapeutic target for type 2 diabetes?Eating and weight disorders : EWD · 2019Review
- Spexin alleviates insulin resistance and inhibits hepatic gluconeogenesis via the FoxO1/PGC-1α pathway in high-fat-diet-induced rats and insulin resistant cells.International journal of biological sciences · 2019Article
- Article
- 10-Hydroxy-2-decenoic acid, a natural product, improves hyperglycemia and insulin resistance in obese/diabetic KK-Ay mice, but does not prevent obesity.The Journal of veterinary medical science · 2017Article
- Sustained NFκB inhibition improves insulin sensitivity but is detrimental to muscle health.Aging cell · 2017Article
- The Cancer Drug Dasatinib Increases PGC-1α in Adipose Tissue but Has Adverse Effects on Glucose Tolerance in Obese Mice.Endocrinology · 2016Article
- Role of PGC-1α in Vascular Regulation: Implications for Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2016Review
- PGC-1α overexpression protects against aldosterone-induced podocyte depletion: role of mitochondria.Oncotarget · 2016Article
- Article
- Complex Coordination of Cell Plasticity by a PGC-1α-controlled Transcriptional Network in Skeletal Muscle.Frontiers in physiology · 2015Review
- Maintaining PGC-1α expression following pressure overload-induced cardiac hypertrophy preserves angiogenesis but not contractile or mitochondrial function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- NHE1 deficiency in liver: implications for non-alcoholic fatty liver disease.Biochemical and biophysical research communications · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Type 2 diabetes is characterized by fasting hyperglycemia, secondary to hepatic insulin resistance and increased glucose production. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator that is thought to control adaptive responses to physiological stimuli. In liver, PGC-1alpha expression is induced by fasting, and this effect promotes gluconeogenesis. To examine whether PGC-1alpha is involved in the pathogenesis of hepatic insulin resistance, we generated transgenic (TG) mice with whole body overexpression of human PGC-1alpha and evaluated glucose homeostasis with a euglycemic-hyperinsulinemic clamp. PGC-1alpha was moderately (approximately 2-fold) overexpressed in liver, skeletal muscle, brain, and heart of TG mice. In liver, PGC-1alpha overexpression resulted in increased expression of hepatocyte nuclear factor-4alpha and the gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. PGC-1alpha overexpression caused hepatic insulin resistance, manifested by higher glucose production and diminished insulin suppression of gluconeogenesis. Paradoxically, PGC-1alpha overexpression improved muscle insulin sensitivity, as evidenced by elevated insulin-stimulated Akt phosphorylation and peripheral glucose disposal. Content of myoglobin and troponin I slow protein was increased in muscle of TG mice, indicating fiber-type switching. PGC-1alpha overexpression also led to lower reactive oxygen species production by mitochondria and reduced IKK/IkappaB signaling in muscle. Feeding a high-fat diet to TG mice eliminated the increased muscle insulin sensitivity. The dichotomous effect of PGC-1alpha overexpression in liver and muscle suggests that PGC-1alpha is a fuel gauge that couples energy demands (muscle) with the corresponding fuel supply (liver). Thus, under conditions of physiological stress (i.e., prolonged fast and exercise training), increased hepatic glucose production may help sustain glucose utilization in peripheral tissues.
Indexed as
Identifiers
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.