Vagal hepatopancreatic reflex effect evoked by intraportal appearance of tGLP-1

Abstract

Among proglucagon-derived peptides, the truncated form of glucagon-like peptide-1, GLP-1(7-36)amide (tGLP-1), is known as the most likely physiological humoral incretin. To examine whether there exists any relationship between tGLP-1 levels in the portal vein and activities of the hepatic and pancreatic vagal system, changes of the impulse discharge rate in the hepatic afferent vagus and the pancreatic efferent vagus upon intraportal tGLP-1 injection were measured in situ in rats anesthetized with urethan and chloralose. First, a 1-min bolus tGLP-1 injection at a periphysiological dose of 0.2 pmol or a pharmacological dose of 4.0 pmol, but not the vehicle injection, significantly facilitated the hepatic vagal afferents for > 90 min, showing weaker facilitation at the 0.05 pmol dose. Notably, the injection of noninsulinotropic full-length GLP-1 failed to facilitate the afferents at the 4.0 or 40.0 pmol dose. Second, the intraportal tGLP-1 injections at the 0.05 and 0.2 pmol dose facilitated marginally and significantly the pancreatic vagal efferents in normal rats, respectively, but had no effect on the hepatic vagotomized rats, even at the 40.0 pmol dose. The present results indicate that an intraportal appearance of tGLP-1 is specifically recognized by the hepatic vagal nerve, and this recognition further augments the pancreatic vagal efferent activity in a reflex way, suggesting another nature of tGLP-1 as neuroincretin in the enteroinsular axis.

The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction

“…41 Finally, it has been proposed that GLP-1 secreted from the intestinal L-cells may act through a direct stimulation of vagal nerve endings in the intestinal wall or in the hepatic circulation. 42 Recent studies have shown that about 50% of the newly secreted GLP-1 is metabolised to its primary metabolite when passing from the intestinal stroma into the capillary bed. 43 Peripheral plasma concentration of GLP-1 may not, therefore, be an adequate measure of the GLP-1 mediated neural signalling in the gut.…”

Synergistic effect of portal glucose and glucagon-like peptide-1 to lower systemic glucose and stimulate counter-regulatory hormones

“…This latter suggestion appears reasonable, as the hepatoportal region has been identified as a locus for one sensing mechanism for glucose [16][17][18]. Moreover, it has been shown that infusion of GLP-1 in the portal vein increases the impulse discharge rate in the vagus nerve [19].…”

Incretin and islet hormonal responses to fat and protein ingestion in healthy men

“…The fact that incretin levels reached their maximal levels and remained elevated after the timing of the insulin response to fat and protein calls into question their primary role as incretin hormones under these conditions, although counterregulatory responses could contribute at the later time points. Furthermore, besides activating insulin secretion through a direct action on ␤-cells, incretins may also stimulate insulin secretion through a neural effect via vagal efferent fibers innervating the pancreas (2,26). Hence, other gut hormones or neural factors affecting insulin release after macronutrient ingestion need to be considered and explored in more detail.…”