Knockdown of GLP-1 receptors in vagal afferents affects normal food intake and glycemia

JP Krieger, M Arnold, KG Pettersen, P Lossel… - Diabetes, 2016 - Am Diabetes Assoc
JP Krieger, M Arnold, KG Pettersen, P Lossel, W Langhans, SJ Lee
Diabetes, 2016Am Diabetes Assoc
Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and
satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral
organs and may contribute to the mediation of gut-derived GLP-1's effects on food intake,
energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron
(VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we
established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector …
Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1’s effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of long-term energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal size and accelerated gastric emptying. Moreover, postmeal glycemia was elevated and insulin release was blunted in GLP-1R kd rats, suggesting that VAN GLP-1Rs are physiological contributors to the neuroincretin effect after a meal. Collectively, our results highlight a crucial role for the VANs in mediating the effects of endogenous GLP-1 on food intake and glycemia and may promote the further development of GLP-1–based therapies.
Am Diabetes Assoc