The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Leptin Impairs Metabolic Actions of Insulin in Isolated Rat Adipocytes
Open accessAbstract
Leptin is an adipocyte hormone involved in the regulation of energy homeostasis. Generally accepted biological effects of leptin are inhibition of food intake and stimulation of metabolic rate in ob/ob mice that are defective in the leptin gene. In contrast to these centrally mediated effects of leptin, we are reporting here on leptin effects on isolated rat adipocytes. Leptin impairs several metabolic actions of insulin, i.e. stimulation of glucose transport, glycogen synthase, lipogenesis, inhibition of isoproterenol-induced lipolysis, and protein kinase A activation, as well as stimulation of protein synthesis. Insulin effects were reduced by leptin (2 nM) with a half-life of about 8 h. At low leptin concentrations (<1 nM), the insulin sensitivity was reduced leading to a shift to the right in the dose-response curve. At higher concentrations the responsiveness was diminished, resulting in nearly complete inhibition of insulin effects at >30 nM leptin. The IC50 value of leptin was 3.1 +/- 1 nM after 15 h of preincubation of adipocytes in primary culture. The natural splice variant des-Gln49-leptin exhibited a significantly lower potency. Adipocytes regained full insulin sensitivity within a few hours after leptin removal. The stimulation of glucose transport by vanadate was not affected by leptin. These data show specific and potent impairment of insulin action by leptin in the physiological concentration range of both leptin and insulin, which may be related to the pathophysiology of insulin resistance in both non-insulin-dependent diabetes mellitus and obesity.
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Cites
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Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0039 · Cited by 2,232
Jung, U., & Choi, M.-S. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15046184 · Cited by 1,880
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Glucose Transporters and Insulin Action — Implications for Insulin Resistance and Diabetes Mellitus
Shepherd, P. R., & Kahn, B. B. (1999) · New England Journal of Medicine · doi:10.1056/nejm199907223410406 · Cited by 1,295
Stern, J. H., Rutkowski, J. M., & Scherer, P. E. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.011 · Cited by 1,031
Metadata
- Authors
- Müller, G., Ertl, J., Gerl, M., & Preibisch, G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-04
- Volume
- 272
- Issue
- 16
- Pages
- 10585-10593
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2096299662
- Cited by
- 450
- References
- 45
- FWCI
- 39.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Müller, G., Ertl, J., Gerl, M., & Preibisch, G. (1997). Leptin Impairs Metabolic Actions of Insulin in Isolated Rat Adipocytes. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.16.10585
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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