Cited by 290Diabetes Treatment and ManagementRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

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Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure

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Hansotia, T., Maida, A., Flock, G., Yamada, Y., Tsukiyama, K., Seino, Y., Drucker, Daniel. J.·2007·Journal of Clinical Investigation

DOI 10.1172/jci25483PMC PMC1705821

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Abstract

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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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.
ORCID: Maida, A.
Yamada, Y.
Seino, Y.
Drucker, Daniel. J.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2007-01-02
Volume: 117
Issue: 1
Pages: 143-152
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci25483
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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Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure

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