The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion
Abstract
Glucagon-like peptide-1 (GLP-1), released from intestinal endocrine L cells, is a potent insulinotropic hormone. GLP-1 secretion is diminished in obese patients. Because obesity is linked to abnormal leptin signaling, we hypothesized that leptin may modulate GLP-1 secretion. Leptin significantly stimulated GLP-1 secretion (by up to 250% of control) from fetal rat intestinal cells, a mouse L cell line (GLUTag), and a human L cell line (NCI-H716) in a dose-dependent manner (P < 0.05–0.001). The long form of the leptin receptor was shown to be expressed, and leptin induced the phosphorylation of STAT3 in the three cell types. The leptin receptor was also expressed by rodent and human intestinal L cells, and leptin (1 mg/kg i.p.) significantly stimulated GLP-1 secretion in rats and ob/ob mice. To determine the effect of leptin resistance on GLP-1 secretion, C57BL/6 mice were fed a high-fat (45%) or low-fat (10%) diet for 8 weeks. Mice on the high-fat diet became obese; developed glucose intolerance, hyperinsulinemia, and hyperleptinemia; and were leptin resistant. Mice on the high-fat diet also had twofold lower basal plasma GLP-1 and a diminished GLP-1 response to oral glucose, by 28.5 ± 5.0% (P < 0.05). These results show for the first time that leptin stimulates GLP-1 secretion from rodent and human intestinal L cells, and they suggest that leptin resistance may account for the decreased levels of GLP-1 found in obese humans.
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Cites
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Cited by
Biology of Incretins: GLP-1 and GIP
Baggio, L. L., & Drucker, D. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.054 · Cited by 3,639
Gastrointestinal regulation of food intake
Cummings, D. E., & Overduin, J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30227 · Cited by 1,216
Cani, P. D., Osto, M., Geurts, L., & Everard, A. (2012) · Gut Microbes · doi:10.4161/gmic.19625 · Cited by 864
The role of incretins in glucose homeostasis and diabetes treatment
Kim, W., & Egan, J. M. (2008) · Pharmacological Reviews · doi:10.1124/pr.108.000604 · Cited by 824
Anxiety, depression, and the microbiome: A role for gut peptides
Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0585-0 · Cited by 573
Metadata
- Authors
- Anini, Y., & Brubaker, P. L.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-02-01
- Volume
- 52
- Issue
- 2
- Pages
- 252-259
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2162826365
- Cited by
- 276
- References
- 9
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- closed
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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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