The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.
Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure
Open accessAbstract
The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) control glucose homeostasis through well-defined actions on the islet beta cell via stimulation of insulin secretion and preservation and expansion of beta cell mass. We examined the importance of endogenous incretin receptors for control of glucose homeostasis through analysis of Glp1r(-/-), Gipr(-/-), and double incretin receptor knockout (DIRKO) mice fed a high-fat (HF) diet. DIRKO mice failed to upregulate levels of plasma insulin, pancreatic insulin mRNA transcripts, and insulin content following several months of HF feeding. Both single incretin receptor knockout and DIRKO mice exhibited resistance to diet-induced obesity, preservation of insulin sensitivity, and increased energy expenditure associated with increased locomotor activity. Moreover, plasma levels of plasminogen activator inhibitor-1 and resistin failed to increase significantly in DIRKO mice after HF feeding, and the GIP receptor agonist [D-Ala(2)]GIP, but not the GLP-1 receptor agonist exendin-4, increased the levels of plasma resistin in studies of both acute and chronic administration. These findings extend our understanding of how endogenous incretin circuits regulate glucose homeostasis independent of the beta cell via control of adipokine secretion and energy expenditure.
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“Combined, the SURPASS and SURMOUNT trials have verified the safety of tirzepatide to be consistent with GLP-1R agonists, along with its enhanced efficacy at maximal doses of 5, 10 and 15 mg (Table 1)132-136,143,145-147”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [147]
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Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
Pharmacology, physiology, and mechanisms of incretin hormone action.
Campbell, J. E., & Drucker, D. J. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.008 · Cited by 1,500
Self-citationAnimal models of obesity and diabetes mellitus
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Metadata
- Authors
- Hansotia, T., Maida, A., Flock, G., Yamada, Y., Tsukiyama, K., Seino, Y., & Drucker, D. J.
- Affiliations
- Mount Sinai Hospital (CA)
- Lunenfeld-Tanenbaum Research Institute (CA)
- Corresponding author
- Drucker, Daniel. J.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-01-02
- Volume
- 117
- Issue
- 1
- Pages
- 143-152
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1705821
- OpenAlex
- W2106984011
- Cited by
- 290
- References
- 36
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 18 · 2023: 10 · 2022: 9 · 2021: 9 · 2020: 12 · 2019: 18 · 2018: 11 · 2017: 16 · 2016: 15 · 2015: 15 · 2014: 9 · 2013: 11 · 2012: 20
- FWCI
- 12.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Diabetes Association
- Canadian Institutes of Health Research
- Banting and Best Diabetes Centre, University of Toronto
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- incretin receptors, GLP-1 receptor, glucose-dependent insulinotropic polypeptide receptor, glucose homeostasis, energy expenditure, diet-induced obesity, high-fat diet, insulin resistance, adipokines, resistin, plasminogen activator inhibitor-1, locomotor activity, exendin-4
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Body Weight, Energy Metabolism, Homeostasis, Insulin, Islets of Langerhans, RNA, Messenger, Transcription, Genetic, Receptors, Glucagon, Mice, Knockout, Mice
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