ArticleThe Journal of clinical investigation2002
Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 147 citations in OpenAlex.
- Adipocyte-specific NR5A2 deficiency ameliorates diet-induced metabolic syndrome by suppressing adipose tissue inflammation.Scientific reports · 2026Article
- High fat diet exacerbated glycolipid metabolism disorder in kidney Yang deficiency rats by interfering with IRS 1-PI3K (p85) -Akt-GLUT 4 pathway.Lipids in health and disease · 2025Article
- Multifunctional Roles and Therapeutic Prospects of C1q/TNF-Related Protein 3 (CTRP3) in Human Diseases.Current medical science · 2025Review
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
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- PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities.Genes & diseases · 2023Review
- Review
- Hepatic overexpression of protein targeting to glycogen attenuates obesity and improves hyperglycemia in db/db mice.Frontiers in endocrinology · 2022Article
- Potential role of microRNAs in selective hepatic insulin resistance: From paradox to the paradigm.Frontiers in endocrinology · 2022Review
- PI3K and AKT at the Interface of Signaling and Metabolism.Current topics in microbiology and immunology · 2022Article
- Lipocalin-2: a role in hepatic gluconeogenesis via AMP-activated protein kinase (AMPK).Journal of endocrinological investigation · 2021Article
- Renal gluconeogenesis in insulin resistance: A culprit for hyperglycemia in diabetes.World journal of diabetes · 2021Review
- Role of Insulin Resistance in MAFLD.International journal of molecular sciences · 2021Review
- Metabolic Role of PTEN in Insulin Signaling and Resistance.Cold Spring Harbor perspectives in medicine · 2020Review
- Basic Mechanisms of Diabetic Heart Disease.Circulation research · 2020Review
- Clinical characteristics of insulin resistance syndromes: A nationwide survey in Japan.Journal of diabetes investigation · 2020Article
- New Insights Into Implications of CTRP3 in Obesity, Metabolic Dysfunction, and Cardiovascular Diseases: Potential of Therapeutic Interventions.Frontiers in physiology · 2020Review
- Role of Hepatic Glucocorticoid Receptor in Metabolism in Models of 5αR1 Deficiency in Male Mice.Endocrinology · 2019Article
- Resolving the Paradox of Hepatic Insulin Resistance.Cellular and molecular gastroenterology and hepatology · 2019Review
- Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice.Diabetologia · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The physiological relevance of phosphoinositide 3-kinase (PI 3-K) signaling in the liver to fuel homeostasis was investigated. Systemic infusion of an adenovirus encoding a dominant negative mutant of PI 3-K ((Delta)p85) resulted in liver-specific expression of this protein and in inhibition of the insulin-induced activation of PI 3-K in the liver within 3 days, without affecting insulin signaling in skeletal muscle. Hepatic expression of (Delta)p85 led to hyperinsulinemia and to a marked increase in blood glucose concentration in response to oral glucose intake. The increases in both glycogen and glucose 6-phosphate content, as well as in Akt and glycogen synthase activities in the liver, that were induced by glucose intake were markedly impaired in mice expressing (Delta)p85. Despite an upregulation of mRNAs for gluconeogenic enzymes apparent in the liver of these animals, the fasting blood glucose concentration was increased only slightly, and the serum concentrations of gluconeogenic precursors were reduced. However, administration of pyruvate, a substrate for gluconeogenesis, resulted in an exaggerated increase in blood glucose concentration. In the fasted state, the mass of adipose tissue of the mice was about 1.5 times that in control mice. The mice also exhibited marked decreases in the serum concentrations of FFAs and triglyceride and suppression of insulin-induced PI 3-K activation in adipose tissue, probably due to the associated hyperinsulinemia. PI 3-K activity in the liver is thus essential for normal carbohydrate and lipid metabolism in living animals.
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