Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes
Open accessAbstract
Adiponectin is intimately involved in the regulation of insulin sensitivity, carbohydrate and lipid metabolism, and cardiovascular functions. The circulating concentration of adiponectin is decreased in obesity and Type 2 diabetes. The present study attempts to elucidate the mechanisms underlying the regulation of adiponectin secretion and expression in rat primary adipocytes. The β-agonist, isoprenaline, decreased adiponectin secretion and expression in a dose-dependent manner in primary adipocytes. Importantly, such an inhibitory effect could be blocked by insulin. The opposing effects of isoprenaline and insulin could be explained by differential regulation of intracellular cAMP levels, since cAMP analogues suppressed adiponectin secretion and expression in a fashion similar to isoprenaline, and insulin blocked the inhibitory effects of the cAMP analogue hydrolysable by PDE (phosphodiesterase). A specific PDE3 inhibitor, milrinone, and PI3K (phosphoinositide 3-kinase) inhibitors abolished the effects of insulin on adiponectin secretion and expression. In the same studies, leptin secretion and expression displayed a similar pattern of regulation to adiponectin. We conclude that insulin and β-agonists act directly at the adipocytes in opposing fashions to regulate the production of adiponectin and leptin, and that a PI3K-PDE3B-cAMP pathway mediates the effects of insulin to restore β-agonist/cAMP-suppressed secretion and expression of these two adipokines.
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Insulin modulates expression of adiponectin, abundance of its receptor in adipose and muscle tissue, and its secretion.
“Likewise, insulin modulates the expression of adiponectin, another well-known adipokine, the abundance of its receptor in adipose and muscle tissue265, 266 as well as its secretion.267, 268”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [267]
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Pancreatic regulation of glucose homeostasis.
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- Authors
- Cong, L., Chen, K., Li, J., Gao, P., Li, Q., Mi, S., Wu, X., & Zhao, A. Z.
- Affiliations
- Department of Cell Biology and Physiology, University of Pittsburgh, S-326, 3500 Terrace Street, Pittsburgh, PA 15261, U.S.A.
- University of Pittsburgh (US)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2007-04-12
- Volume
- 403
- Issue
- 3
- Pages
- 519-525
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1876381
- OpenAlex
- W1976974669
- Cited by
- 62
- References
- 38
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 2 · 2016: 3 · 2015: 3 · 2014: 8 · 2013: 3 · 2012: 2
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5r01dk064383-04)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK064383, R01 DK064383-01)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- adiponectin, leptin, insulin, adipocytes, phosphatidylinositol 3-kinase, PDE3B, cAMP signaling, isoproterenol, beta-adrenergic agonists, adipokine secretion, milrinone, type 2 diabetes, obesity
- MeSH terms
- Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Adrenergic beta-Agonists, Androstadienes, Animals, Chromones, Insulin, Isoproterenol, Male, Morpholines, 3',5'-Cyclic-AMP Phosphodiesterases, 8-Bromo Cyclic Adenosine Monophosphate, Rats, Sprague-Dawley, Adipocytes, Milrinone, Leptin, Rats, Adiponectin, Cyclic Nucleotide Phosphodiesterases, Type 3
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