ArticleCell metabolism2025
Spatial regulation of glucose and lipid metabolism by hepatic insulin signaling.
Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Review
- Review
- Liver endothelial zonation orchestrates hepatic steatosis onset through retinoic acid-regulated FGF1.Science advances · 2026Article
- Liver sinusoidal endothelial cell fenestrations in metabolic liver disease: from molecular mechanisms to therapeutic perspectives.Cell communication and signaling : CCS · 2026Review
- SLC27A1 overexpression correlates with lactylation and poor colorectal cancer progression.Scientific reports · 2026Article
- [Research advances on hepatocyte zonal changes in metabolic associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Dysregulation of the AMPK-SREBP1-FASN axis in MASLD: driving a vicious cycle of lipotoxicity and metabolic-immune crosstalk.Lipids in health and disease · 2026Review
- Heart-liver co-management: epidemiology, mechanisms, and novel therapeutic approaches for metabolic dysfunction-associated steatotic liver disease and coronary artery disease.Frontiers in cardiovascular medicine · 2026Review
- Metabolic dysfunction-associated steatotic liver disease as a systemic disorder: extrahepatic manifestations and the need for data-driven phenotyping.Frontiers in endocrinology · 2026Review
- Diagnostic Performance of Six Insulin Resistance Indices for MAFLD Across BMI Categories in Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Regulatory effects of hawthorn on lipid metabolic homeostasis: mechanisms, evidences, and perspectives.Frontiers in nutrition · 2026Review
- Taurodeoxycholic, taurocholic, and glycocholic acids promote hepatic gluconeogenesis via TGR5 in dairy cows.Journal of animal science and biotechnology · 2025Article
- Mitochondrial dysfunction and metabolic reprogramming in acute kidney injury: mechanisms, therapeutic advances, and clinical challenges.Frontiers in physiology · 2025Review
- Roles of chemical species transport and transformation in the biophysics of human pathophysiology.npj biological physics and mechanics · 2025Review
- ISIFrontiers in medicine · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Hepatic insulin sensitivity is critical for systemic glucose and lipid homeostasis. The liver is spatially organized into zones in which hepatocytes express distinct metabolic enzymes; however, the functional significance of this zonation to metabolic dysregulation caused by insulin resistance is undetermined. Here, we used CreER mice to selectively disrupt insulin signaling in periportal (PP) and pericentral (PC) hepatocytes. PP-insulin resistance has been suggested to drive combined hyperglycemia and excess lipogenesis in individuals with type 2 diabetes. However, PP-insulin resistance in mice impaired lipogenesis and suppressed high-fat diet (HFD)-induced hepatosteatosis, despite elevated gluconeogenesis and insulin. In contrast, PC-insulin resistance reduced HFD-induced PC steatosis while preserving normal glucose homeostasis, in part by shifting glycolytic metabolism from the liver to the muscle. These results demonstrate distinct roles of insulin in PP versus PC hepatocytes and suggest that PC-insulin resistance might be therapeutically useful to combat hepatosteatosis without compromising glucose homeostasis.
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