ArticleThe Biochemical journal2020
Regulation of basal expression of hepatic PEPCK and G6Pase by AKT2.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Hypoxia Promotes Gluconeogenesis Through PGC-1α in the Liver of Lasiopodomys brandtii.Integrative zoology · 2026Article
- Antidiabetic Properties ofLife (Basel, Switzerland) · 2026Review
- A Herbal Pair ofFood science & nutrition · 2026Article
- Lack of GPNMB Is Associated With Altered Lipid and Glucose Metabolism and Disrupted Diurnal Hepatic Glycogen Regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Regulation of metabolic pathways genes and the effects of very low-calorie diet on insulin resistance and fatty acid profiles in obese patients undergoing bariatric surgery.Journal of diabetes and metabolic disorders · 2025Article
- The Lactate-Primed KAT8‒PCK2 Axis Exacerbates Hepatic Ferroptosis During Ischemia/Reperfusion Injury by Reprogramming OXSM-Dependent Mitochondrial Fatty Acid Synthesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- High carbohydrate diet programs metabolic enzyme gene expression modification in F2 generation wistar rat males.Current research in physiology · 2025Article
- Chemical Composition, Molecular Docking Analysis, and Biological Properties ofAdvanced biomedical research · 2025Article
- Network Pharmacology Analysis, Molecular Docking Integrated Experimental Verification Reveal the Mechanism ofCurrent issues in molecular biology · 2024Article
- Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Vitamin D improves the antidiabetic effectiveness of aerobic training via modulation of Akt, PEPCK, and G6Pase expression.Diabetology & metabolic syndrome · 2023Article
- Theabrownin from Dark Tea Ameliorates Insulin Resistance via Attenuating Oxidative Stress and Modulating IRS-1/PI3K/Akt Pathway in HepG2 Cells.Nutrients · 2023Article
- HMC Ameliorates Hyperglycemia via Acting PI3K/AKT Pathway and Improving FOXO1 Pathway in ob/ob Mice.Nutrients · 2023Article
- Diabetes and diabesity in the view of proteomics, drug, and plant-derived remedies.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2023Review
- From Diabetes Care to Heart Failure Management: A Potential Therapeutic Approach Combining SGLT2 Inhibitors and Plant Extracts.Nutrients · 2022Review
- Anti-hyperglycemic effects of Eryngium billardierei F. Delaroche extract on insulin-resistance HepG2 cells in vitro.Molecular biology reports · 2022Article
- Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.Frontiers in oncology · 2022Review
- PTEN Deletion in Adult Mice Induces Hypoinsulinemia With Concomitant Low Glucose Levels.Frontiers in endocrinology · 2022Article
- Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR.The American journal of pathology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic glucose metabolism signaling downstream of insulin can diverge to multiple pathways including AKT. Genetic studies suggest that AKT is necessary for insulin to suppress gluconeogenesis. To specifically address the role of AKT2, the dominant liver isoform of AKT in the regulation of gluconeogenesis genes, we generated hepatocytes lacking AKT2 (Akt2-/-). We found that, in the absence of insulin signal, AKT2 is required for maintaining the basal level expression of phosphoenolpyruvate carboxyl kinase (PEPCK) and to a lesser extent G6Pase, two key rate-limiting enzymes for gluconeogenesis that support glucose excursion due to pyruvate loading. We further showed that this function of AKT2 is mediated by the phosphorylation of cyclic AMP response element binding (CREB). Phosphorylation of CREB by AKT2 is needed for CREB to induce the expression of PEPCK and likely represents a priming event for unstimulated cells to poise to receive glucagon and other signals. The inhibition of gluconeogenesis by insulin is also dependent on the reduced FOXO1 transcriptional activity at the promoter of PEPCK. When insulin signal is absent, this activity appears to be inhibited by AKT2 in manner that is independent of its phosphorylation by AKT. Together, this action of AKT2 on FOXO1 and CREB to maintain basal gluconeogenesis activity may provide fine-tuning for insulin and glucocorticoid/glucagon to regulate gluconeogenesis in a timely manner to meet metabolic needs.
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Registered trials
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