Abstract
Stimulation of glucagon-like peptide-1 (GLP-1) receptors increases the insulin release in the pancreas during high glucose levels, and also stimulates a feeling of satiety. Likewise, synthetic GLP-1 receptor agonists derived from exendin are used successfully in the treatment of type-2 diabetes mellitus and obesity. Interestingly, preclinical and clinical studies further suggest that GLP-1 receptor agonists may decrease motor, behavioral, and cognitive symptoms in (animal models) Parkinson’s disease and Alzheimer’s disease and may slow down neurodegeneration. These observations suggest stimulation of GLP-1 receptors in the brain. The GLP-1 positron emission tomography (PET) tracer 68Ga-NODAGA-exendin-4 has been developed and successfully used for imaging in humans. In an ongoing study on the effects of bariatric surgery on GLP-1 receptor expression, we performed 68Ga-NODAGA-exendin-4 PET in obese subjects. Here we evaluated whether GLP-1 receptor binding could be visualized in the central nervous system in 10 obese subjects (seven woman; body mass index: mean ± SD: 39 ± 4.4 kg/m2) before bariatric surgery. Although we observed clear uptake in the pituitary area (mean SUVmax 4.3 ± 2.3), we found no significant uptake in other parts of the brain. We conclude that 68Ga-NODAGA-exendin-4 PET cannot be used to analyze GLP-1 receptors in the brain of obese subjects.
Highlights
Glucagon-like peptide-1 (GLP-1) is predominantly synthesized in enteroendocrine cells of the distal small intestine and secreted in the blood when food enters the duodenum
We demonstrated the ability of 68 Ga-NODAGA-exendin-4 to visualize glucagon-like peptide-1 (GLP-1) receptor expression on pancreatic beta cells [31]
Participating subjects were eligible for the present analysis if they underwent wholebody 68 Ga-NODAGA-exendin-4 positron emission tomography (PET) imaging before surgery
Summary
Glucagon-like peptide-1 (GLP-1) is predominantly synthesized in enteroendocrine cells of the distal small intestine and secreted in the blood when food enters the duodenum (for a recent review, see Mori et al [1]). GLP-1 belongs to the incretin family (INtestinal seCRETion of INSulin). GLP-1 is synthesized in the brain, and in the nucleus tractus solitarius, which is located in the brainstem [3]. These GLP-1 expressing neurons extend to parts of the hypothalamus, the paraventricular nucleus and arcuate nucleus [4]. Synthetic GLP-1 receptor agonists are used successfully in the treatment of type-2 diabetes mellitus and to reduce overweight in obesity
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