ArticleDiabetologia2011
Time-dependent effects of Prkce deletion on glucose homeostasis and hepatic lipid metabolism on dietary lipid oversupply in mice.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
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- Nonalcoholic Fatty Liver Disease and Staging of Hepatic Fibrosis.Advances in experimental medicine and biology · 2024Review
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- Genome-wide association study and genomic prediction for intramuscular fat content in Suhuai pigs using imputed whole-genome sequencing data.Evolutionary applications · 2022Article
- Differential Circular RNA Expression Profiling of Orbital Connective Tissue From Patients With Type I and Type II Thyroid-Associated Ophthalmopathy.Investigative ophthalmology & visual science · 2022Article
- Insulin Resistance: From Mechanisms to Therapeutic Strategies.Diabetes & metabolism journal · 2022Review
- Concerted regulation of non-alcoholic fatty liver disease progression by microRNAs in apolipoprotein E-deficient mice.Disease models & mechanisms · 2021Article
- Dietary carbohydrates and fats in nonalcoholic fatty liver disease.Nature reviews. Gastroenterology & hepatology · 2021Review
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- A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance.Cell metabolism · 2020Article
- Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.Lipids in health and disease · 2020Review
- Cardio-Metabolic Effects of High-Fat Diets and Their Underlying Mechanisms-A Narrative Review.Nutrients · 2020Review
- Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease.Journal of clinical and translational hepatology · 2019Review
- Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes.Current diabetes reports · 2019Review
- Hepatic miR‑215 target Rictor and modulation of hepatic insulin signalling in rats.Molecular medicine reports · 2019Article
- Emerging Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease, Insulin Resistance, and Type 2 Diabetes.Annual review of pharmacology and toxicology · 2019Review
- Mechanisms of Insulin Action and Insulin Resistance.Physiological reviews · 2018Review
- Anarchy in the UPR: A CaBioscience reports · 2018Article
- Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisWe examined the time-dependent effects of deletion of the gene encoding protein kinase C epsilon (Prkce) on glucose homeostasis, insulin secretion and hepatic lipid metabolism in fat-fed mice.
methodsPrkce(-/-) and wild-type (WT) mice were fed a high-fat diet for 1 to 16 weeks and subjected to i.p. glucose tolerance tests (ipGTT) and indirect calorimetry. We also investigated gene expression and protein levels by RT-PCR, quantitative protein profiling (isobaric tag for relative and absolute quantification; iTRAQ) and immunoblotting. Lipid levels, mitochondrial oxidative capacity and lipid metabolism were assessed in liver and primary hepatocytes.
resultsWhile fat-fed WT mice became glucose intolerant after 1 week, Prkce(-/-) mice exhibited normal glucose and insulin levels. iTRAQ suggested differences in lipid metabolism and oxidative phosphorylation between fat-fed WT and Prkce(-/-) animals. Liver triacylglycerols were increased in fat-fed Prkce(-/-) mice, resulting from altered lipid partitioning which promoted esterification of fatty acids in hepatocytes. In WT mice, fat feeding elevated oxygen consumption in vivo and in isolated liver mitochondria, but these increases were not seen in Prkce(-/-) mice. Prkce(-/-) hepatocytes also exhibited reduced production of reactive oxygen species (ROS) in the presence of palmitate. After 16 weeks of fat feeding, however, the improved glucose tolerance in fat-fed Prkce(-/-) mice was instead associated with increased insulin secretion during ipGTT, as we have previously reported. CONCLUSIONS/
interpretationPrkce deletion ameliorates diet-induced glucose intolerance via two temporally distinct phenotypes. Protection against insulin resistance is associated with changes in hepatic lipid partitioning, which may reduce the acute inhibitory effects of fatty acid catabolism, such as ROS generation. In the longer term, enhancement of glucose-stimulated insulin secretion prevails.
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