ArticleProceedings of the National Academy of Sciences of the United States of America2009
Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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95 citing papers in PubMed, 186 citations in OpenAlex.
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis.Cell reports. Medicine · 2024Article
- Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation.Cell chemical biology · 2024Article
- DNA Methylation-derived biological age and long-term mortality risk in subjects with type 2 diabetes.Cardiovascular diabetology · 2024Article
- Hepatic glucose metabolism in the steatotic liver.Nature reviews. Gastroenterology & hepatology · 2024Review
- Review
- The Perfect Cup? Coffee-Derived Polyphenols and Their Roles in Mitigating Factors Affecting Type 2 Diabetes Pathogenesis.Molecules (Basel, Switzerland) · 2024Review
- Tyrosol-loaded Nano-niosomes Attenuate Diabetic Injury by TargetingGlucose Metabolism, Inflammation, and Glucose Transfer.Pharmaceutical nanotechnology · 2024Article
- Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism.Cell metabolism · 2023Article
- Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice.Nature communications · 2023Article
- Gastric Bypass Regulates Early Inflammatory Responses in High-Fat Diet-Induced Obese Mice.The Journal of surgical research · 2022Article
- Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism.iScience · 2022Article
- TOX4, an insulin receptor-independent regulator of hepatic glucose production, is activated in diabetic liver.Cell metabolism · 2022Article
- An integrative transcriptional logic model of hepatic insulin resistance.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model.Scientific reports · 2021Article
- Metformin - its anti-cancer effects in hematologic malignancies.Oncology reviews · 2021Article
- Cellular and Molecular Mechanisms of Metformin Action.Endocrine reviews · 2021Review
- Tracking the carbons supplying gluconeogenesis.The Journal of biological chemistry · 2020Review
- Loss of TSC complex enhances gluconeogenesis via upregulation ofProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Protective effect of ganoderic acid against the streptozotocin induced diabetes, inflammation, hyperlipidemia and microbiota imbalance in diabetic rats.Saudi journal of biological sciences · 2019Article
35 more citing papers are in PubMed but not listed here.
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8 authors at 3 institutions in 1 country.
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Abstract
Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). To test this hypothesis, we examined hepatic expression of these 2 key gluconeogenic enzymes in 2 rodent models of fasting hyperglycemia and in patients with T2DM. In rats, high-fat feeding (HFF) induces insulin resistance but a robust beta-cell response prevents hyperglycemia. Fasting hyperglycemia was induced in the first rat model by using nicotinamide and streptozotocin to prevent beta-cell compensation, in combination with HFF (STZ/HFF). In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. Finally, the expression of these enzymes was measured in liver biopsy samples obtained from insulin sensitive, insulin resistant, and untreated T2DM patients undergoing bariatric surgery. Rats treated with STZ/HFF developed modest fasting hyperglycemia (119 +/- 4 vs. 153 +/- 6 mg/dL, P < 0.001) and increased rates of endogenous glucose production (EGP) (4.6 +/- 0.6 vs. 6.9 +/- 0.6 mg/kg/min, P = 0.02). Surprisingly, the expression of PEPCK or G6Pc was not increased. Matching plasma insulin and glucagon with portal infusions led to higher plasma glucoses in the HFF rats (147 +/- 4 vs. 161 +/- 4 mg/dL, P = 0.05) with higher rates of EGP and gluconeogenesis. However, PEPCK and G6Pc expression remained unchanged. Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM.
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