ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Modeling of free fatty acid dynamics: insulin and nicotinic acid resistance under acute and chronic treatments.Journal of pharmacokinetics and pharmacodynamics · 2017Pooled it
- Niacin induces miR-502-3p expression which impairs insulin sensitivity in human adipocytes.International journal of obesity (2005) · 2019Trial
- Diet and Lifestyle Interventions in Metabolic Dysfunction-Associated Fatty Liver Disease: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Association of dietary niacin intake with all-cause and cardiovascular mortality: National Health and Nutrition Examination Survey (NHANES) 2003-2018.Scientific reports · 2024Article
- Association of niacin intake and metabolic dysfunction-associated steatotic liver disease: findings from National Health and Nutrition Examination Survey.BMC public health · 2024Article
- B Vitamins, Glucoronolactone and the Immune System: Bioavailability, Doses and Efficiency.Nutrients · 2023Review
- Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation.PloS one · 2023Article
- The TBK1/IKKε inhibitor amlexanox improves dyslipidemia and prevents atherosclerosis.JCI insight · 2022Article
- NADAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Review
- Drugs Interfering with Insulin Resistance and Their Influence on the Associated Hypermetabolic State in Severe Burns: A Narrative Review.International journal of molecular sciences · 2021Review
- Vitamins and non-alcoholic fatty liver disease: A Molecular InsightLiver research (Beijing, China) · 2021Article
- The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism.International journal of molecular sciences · 2021Article
- Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A).Annals of human genetics · 2021Article
- Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue.International journal of endocrinology · 2018Review
- Nutrient Restriction Increases Circulating and Hepatic Ceramide in Dairy Cows Displaying Impaired Insulin Tolerance.Lipids · 2017Article
- The Role of Vitamins in the Pathogenesis of Non-alcoholic Fatty Liver Disease.Integrative medicine insights · 2016Review
- Dosing profile profoundly influences nicotinic acid's ability to improve metabolic control in rats.Journal of lipid research · 2015Article
- Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile.Journal of lipid research · 2014Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the underlying mechanisms are poorly understood. The current study addressed the effects of long-term niacin treatment on insulin-mediated inhibition of adipocyte lipolysis and focused on the regulation of cAMP levels. APOE*3-Leiden.CETP transgenic mice treated with niacin for 15 wk were subjected to an insulin tolerance test and showed whole body insulin resistance. Similarly, adipocytes isolated from niacin-treated mice were insulin resistant and, interestingly, exhibited an increased response to cAMP stimulation by 8Br-cAMP, β1- and β2-adrenergic stimulation. Gene expression analysis of the insulin and β-adrenergic pathways in adipose tissue indicated that all genes were downregulated, including the gene encoding the cAMP-degrading enzyme phosphodiesterase 3B (PDE3B). In line with this, we showed that insulin induced a lower PDE3B response in adipocytes isolated from niacin-treated mice. Inhibiting PDE3B with cilostazol increased lipolytic responsiveness to cAMP stimulation in adipocytes. These data show that long-term niacin treatment leads to a downregulation of PDE3B in adipocytes, which could explain part of the observed insulin resistance and the increased responsiveness to cAMP stimulation.
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