J.S. ten Kulve
L. van Bloemendaal
S.E. la Fleur
- Decreased Hypothalamic Glucagon-Like Peptide-1 Receptor Expression in Type 2 Diabetes Patients
- Journal of clinical endocrinology and metabolism
- Volume | Issue number
- 101 | 5
- Pages (from-to)
- Document type
- Faculty of Social and Behavioural Sciences (FMG)
- Psychology Research Institute (PsyRes)
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.
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.
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.
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.
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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