Decreased Hypothalamic Glucagon-Like Peptide-1 Receptor Expression in Type 2 Diabetes Patients
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CONTEXT: Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonist treatment in type 2 diabetes (T2DM) reduce blood glucose and food intake. It has been suggested that these effects are partly mediated through central GLP-1 receptors (GLP-1Rs). The rodent and nonhuman primate hypothalamus show clear GLP-1R expression. However, a detailed description of GLP-1R expression in the human hypothalamus is lacking, and it is unknown whether this expression is altered in T2DM patients. OBJECTIVE: The objective of the study was to investigate the GLP-1R distribution in the human postmortem hypothalamus and to determine whether hypothalamic GLP-1R expression is altered in T2DM patients. DESIGN: We investigated the distribution of GLP-1R expression throughout the human hypothalamus by means of in situ hybridization. We also performed quantifications of GLP-1R mRNA expression in two hypothalamic nuclei (ie, the paraventricular nucleus [PVN] and infundibular nucleus [IFN]), comparing patients with T2DM and control subjects. RESULTS: We found that GLP-1R mRNA was expressed in a number of hypothalamic nuclei including the PVN and the IFN, both involved in the regulation of energy metabolism. We observed sporadic colocalization of the GLP-1R in the IFN with the orgexigenic neuropeptide Y, agouti-related peptide, or proopiomelanocortin transcripts. Comparison of GLP-1R mRNA in the PVN and IFN between T2DM patients and control subjects revealed a decreased expression in T2DM patients. CONCLUSIONS: Our studies show that GLP-1R is widely expressed throughout the human hypothalamus. The decreased expression of GLP-1R in the PVN and IFN of T2DM patients may be related to the dysregulation of feeding behavior and glucose homeostasis in T2DM.
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GLP-1R is downregulated in the hypothalamus of T2D patients compared with healthy controls.
“Interestingly, GLP-1R is downregulated in the hypothalamus of T2D patients in comparison to healthy controls, suggesting that the reduced ability of GLP-1 to induce satiety may contribute to the dysfunctional feeding behaviours and metabolic homeostasis observed in these patients.226”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [226]
Reduced ability of GLP-1 to induce satiety may contribute to dysfunctional feeding behaviours and metabolic homeostasis in T2D patients.
“Interestingly, GLP-1R is downregulated in the hypothalamus of T2D patients in comparison to healthy controls, suggesting that the reduced ability of GLP-1 to induce satiety may contribute to the dysfunctional feeding behaviours and metabolic homeostasis observed in these patients.226”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [226]
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- Authors
- ten Kulve, J. S., van Bloemendaal, L., Balesar, R., IJzerman, R. G., Swaab, D. F., Diamant, M., la Fleur, S. E., & Alkemade, A.
- Affiliations
- Royal Netherlands Academy of Arts and Sciences (NL)
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- Alkemade, Anneke
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-05
- Volume
- 101
- Issue
- 5
- Pages
- 2122-2129
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2210361886
- Cited by
- 54
- References
- 28
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 5
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion, other-oa)
- Funders
- Universiteit van Amsterdam
- Amsterdam Brain and Cognition
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- GLP-1 receptor, type 2 diabetes, hypothalamus, paraventricular nucleus, arcuate nucleus, neuropeptide Y, agouti-related protein, proopiomelanocortin, feeding behavior, glucose homeostasis, energy metabolism
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Aged, Aged, 80 and over, Arcuate Nucleus of Hypothalamus, Diabetes Mellitus, Type 2, Female, Humans, Hypothalamus, Male, Middle Aged, Neuropeptide Y, Paraventricular Hypothalamic Nucleus, Pro-Opiomelanocortin, Agouti-Related Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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