ArticleDiabetes2009
Cleavage of protein kinase D after acute hypoinsulinemia prevents excessive lipoprotein lipase-mediated cardiac triglyceride accumulation.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Global knockout of VEGFB improves lipoprotein lipase activity leading to an improved lipid profile during diabetes.Frontiers in pharmacology · 2026Article
- Lipoprotein lipase as a target for obesity/diabetes related cardiovascular disease.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Flow-Induced Secretion of Endothelial Heparanase Regulates Cardiac Lipoprotein Lipase and Changes Following Diabetes.Journal of the American Heart Association · 2022Article
- Characterization of lipoprotein lipase storage vesicles in 3T3-L1 adipocytes.Journal of cell science · 2022Article
- Decoding the Cardiac Actions of Protein Kinase D Isoforms.Molecular pharmacology · 2021Review
- Lipoprotein Lipase and Its Delivery of Fatty Acids to the Heart.Biomolecules · 2021Review
- Function and Regulation of Protein Kinase D in Oxidative Stress: A Tale of Isoforms.Oxidative medicine and cellular longevity · 2018Review
- Targeting viperin improves diet-induced glucose intolerance but not adipose tissue inflammation.Oncotarget · 2017Article
- Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System.Frontiers in pharmacology · 2017Review
- β-adrenergic signaling inhibits Gq-dependent protein kinase D activation by preventing protein kinase D translocation.Circulation research · 2014Article
- Regulatory domain determinants that control PKD1 activity.The Journal of biological chemistry · 2012Article
- Regulation of protein kinase D1 activity.Molecular pharmacology · 2012Review
- New wrinkles in lipoprotein lipase biology.Current opinion in lipidology · 2012Review
- Severity of diabetes governs vascular lipoprotein lipase by affecting enzyme dimerization and disassembly.Diabetes · 2011Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDuring hypoinsulinemia, when cardiac glucose utilization is impaired, the heart rapidly adapts to using more fatty acids. One means by which this is achieved is through lipoprotein lipase (LPL). We determined the mechanisms by which the heart regulates LPL after acute hypoinsulinemia. RESEARCH DESIGN AND
methodsWe used two different doses of streptozocin (55 [D-55] and 100 [D-100] mg/kg) to induce moderate and severe hypoinsulinemia, respectively, in rats. Isolated cardiomyocytes were also used for transfection or silencing of protein kinase D (PKD) and caspase-3.
resultsThere was substantial increase in LPL in D-55 hearts, an effect that was absent in severely hypoinsulinemic D-100 animals. Measurement of PKD, a key element involved in increasing LPL, revealed that only D-100 hearts showed an increase in proteolysis of PKD, an effect that required activation of caspase-3 together with loss of 14-3-3zeta, a binding protein that protects enzymes against degradation. In vitro, phosphomimetic PKD colocalized with LPL in the trans-golgi. PKD, when mutated to prevent its cleavage by caspase-3 and silencing of caspase-3, was able to increase LPL activity. Using a caspase inhibitor (Z-DEVD) in D-100 animals, we effectively lowered caspase-3 activity, prevented PKD cleavage, and increased LPL vesicle formation and translocation to the vascular lumen. This increase in cardiac luminal LPL was associated with a striking accumulation of cardiac triglyceride in Z-DEVD-treated D-100 rats. CONCLUSIONS After severe hypoinsulinemia, activation of caspase-3 can restrict LPL translocation to the vascular lumen. When caspase-3 is inhibited, this compensatory response is lost, leading to lipid accumulation in the heart.
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