GLP-1 induces alpha cell proliferation and overrides leptin suppression induced by negative energy balance in vagotomized rats.

Authors:
Tiago Morais
Tiago Morais
Portugal Department of EndocrinologyHospital S.João
Portugal
Sara Andrade
Sara Andrade
Institute of Biology
Brazil
Felipe F Casanueva
Felipe F Casanueva
The University of Manchester
United Kingdom
Mariana P Monteiro
Mariana P Monteiro
University of Porto
Portugal

J Cell Biochem 2019 Apr 17. Epub 2019 Apr 17.

Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.

Glucagon-like peptide-1 (GLP-1) influences energy balance by exerting effects on food intake and glucose metabolism, through mechanisms that are partially dependent on the vagal pathway. The aim of this study was to characterize the effects of chronic GLP-1 stimulation on energy homeostasis and glucose metabolism in the absence of vagal innervation Truncal vagotomized (VGX) and sham operated rats (SHAM) received an intraperitoneal GLP-1 infusion (3.5 pmol/kg/min) trough mini-osmotic pumps. To dissect the effects derived from vagal denervation on food intake, an additional group was included consisting of sham operated rats that were PAIR FED to VGX. Food intake and body weight were recorded throughout the experimental period, while the percentage of white and brown adipose tissue, fasting glucose, insulin, gastro-intestinal hormonal profile, hypothalamic, and BAT gene expression were assessed at endpoint. VGX rats had significantly lower food intake, body weight gain, and leptin levels when compared with SHAM rats. Despite having similar body weight, PAIR-FED rats had lower fasting leptin, insulin and insulin resistance, while having higher ghrelin levels than VGX. GLP-1 infusion did not influence food intake or body weight, but was associated with lower leptin levels in VGX and lower pancreatic α-cells ki-67 staining in SHAM. Concluding, this study corroborates that the vagus nerve may modulate whole body energy homeostasis by acting in peripheral signals. Our data suggest that in the absence of vagal or parasympathetic tonus, GLP-1 mediated inhibition of cell proliferation markers in α-cells is prevented, meanwhile leptin suppression, associated with a negative energy balance, is partially overridden.

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http://dx.doi.org/10.1002/jcb.28719DOI Listing
April 2019
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References

(Supplied by CrossRef)
The versatile role of the vagus nerve in the gastrointestinal tract
Stakenborg N et al.
EMJ Gastroenterol 2013
Biology of incretins: GLP‐1 and GIP
Baggio LL et al.
Gastroenterology 2007
Glucagon‐like peptide‐1 inhibits gastric emptying via vagal afferent‐mediated central mechanisms
Imeryuz N et al.
Am J Physiol 1997

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