ArticleDiabetes2009
Nutrient stress activates inflammation and reduces glucose metabolism by suppressing AMP-activated protein kinase in the heart.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Autophagy as a therapeutic target in diabetic nephropathy.Experimental diabetes research · 2012Pooled it
- Acute metabolic effects of cannabinoid receptor modulators during sequential hyperglycemic, euglycemic-hyperinsulinemic clamps in healthy individuals.American journal of physiology. Endocrinology and metabolism · 2026Trial
- Molecular Basis of Adipose-Cardiac Crosstalk in Cardiovascular Diseases: From Mechanisms to Therapeutic Opportunities.Biomolecules · 2026Review
- PPARα-NF-κB heterodimer mediates obesity-induced diastolic dysfunction through autocrine production of IL-6.The Journal of clinical investigation · 2026Article
- An IL6 variant -174 G-C alters cardiac hypertrophy but not cardiometabolic responses to HFD in mice.npj metabolic health and disease · 2026Article
- The crosstalk between immune activation and metabolism in heart failure. A scientific statement of the Heart Failure Association of the ESC.European journal of heart failure · 2025Review
- Obesity accelerates cardiovascular ageing.European heart journal · 2025Review
- Molecular Insights into Ischemia-Reperfusion Injury in Coronary Artery Disease: Mechanisms and Therapeutic Implications: A Comprehensive Review.Antioxidants (Basel, Switzerland) · 2025Review
- Role of AMPK and Sirtuins in Aging Heart: Basic and Translational Aspects.Aging and disease · 2024Review
- Obesity Arrhythmias: Role of IL-6 Trans-Signaling.International journal of molecular sciences · 2024Review
- Article
- Inflammatory Mechanisms in Heart Failure with Preserved Ejection Fraction.Physiology (Bethesda, Md.) · 2023Review
- Free fatty acids induce coronary microvascular dysfunction via inhibition of the AMPK/KLF2/eNOS signaling pathway.International journal of molecular medicine · 2023Article
- Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism.Journal of translational medicine · 2023Article
- Article
- Puerarin Attenuates High-Glucose and High-Lipid-Induced Inflammatory Injury in H9c2 Cardiomyocytes via CAV3 Protein Upregulation.Journal of inflammation research · 2023Article
- Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease.Advanced pharmaceutical bulletin · 2023Review
- The ciliary protein Spef2 stimulates acinar Ampkα/Sirt1 signaling and ameliorates acute pancreatitis and associated lung injury.Annals of translational medicine · 2022Article
- Profile of crosstalk between glucose and lipid metabolic disturbance and diabetic cardiomyopathy: Inflammation and oxidative stress.Frontiers in endocrinology · 2022Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHeart failure is a major cause of mortality in diabetes and may be causally associated with altered metabolism. Recent reports indicate a role of inflammation in peripheral insulin resistance, but the impact of inflammation on cardiac metabolism is unknown. We investigated the effects of diet-induced obesity on cardiac inflammation and glucose metabolism in mice. RESEARCH DESIGN AND
methodsMale C57BL/6 mice were fed a high-fat diet (HFD) for 6 weeks, and heart samples were taken to measure insulin sensitivity, glucose metabolism, and inflammation. Heart samples were also examined following acute interleukin (IL)-6 or lipid infusion in C57BL/6 mice and in IL-6 knockout mice following an HFD.
resultsDiet-induced obesity reduced cardiac glucose metabolism, GLUT, and AMP-activated protein kinase (AMPK) levels, and this was associated with increased levels of macrophages, toll-like receptor 4, suppressor of cytokine signaling 3 (SOCS3), and cytokines in heart. Acute physiological elevation of IL-6 suppressed glucose metabolism and caused insulin resistance by increasing SOCS3 and via SOCS3-mediated inhibition of insulin receptor substrate (IRS)-1 and possibly AMPK in heart. Diet-induced inflammation and defects in glucose metabolism were attenuated in IL-6 knockout mice, implicating the role of IL-6 in obesity-associated cardiac inflammation. Acute lipid infusion caused inflammation and raised local levels of macrophages, C-C motif chemokine receptor 2, SOCS3, and cytokines in heart. Lipid-induced cardiac inflammation suppressed AMPK, suggesting the role of lipid as a nutrient stress triggering inflammation.
conclusionsOur findings that nutrient stress activates cardiac inflammation and that IL-6 suppresses myocardial glucose metabolism via inhibition of AMPK and IRS-1 underscore the important role of inflammation in the pathogenesis of diabetic heart.
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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.