Intestinal lymph as a readout of meal-induced GLP-1 release in an unrestrained rat model

Abstract

Intestinal lymph supposedly provides a readout for the secretion of intestinal peptides. We here assessed how mesenteric lymph duct (MLD) lymph levels of glucagon-like peptide (GLP-1), insulin, and metabolites [glucose and triglycerides (TG)] evolve after isocaloric high- and low-fat diet (HFD and LFD) meals and how they compare with hepatic portal vein (HPV) plasma levels. Moreover, we examined the effects of intraperitoneally administered GLP-1 (1 or 10 nmol/kg) on these parameters. At 20 min after the HFD meal onset, GLP-1 levels were higher in MLD lymph than in HPV plasma. No such difference occurred with the LFD meal. Intraperitoneal injections of 10 nmol/kg GLP-1 before meals enhanced the meal-induced increases in MLD lymph and HPV plasma GLP-1 levels except for the MLD lymph levels after the HFD meal. Intraperitoneal injection of 1 nmol/kg GLP-1 only increased HPV plasma GLP-1 levels at 60 min after the HFD meal. GLP-1 injections did not increase the MLD lymph or HPV plasma GLP-1 concentrations beyond the physiological range, suggesting that intraperitoneal GLP-1 injections can recapitulate the short-term effects of endogenous GLP-1. Dipeptidyl peptidase IV (DPP-IV) activity in MLD lymph was lower than in HPV plasma, which presumably contributed to the higher levels of GLP-1 in lymph than in plasma. Insulin and glucose showed similar profiles in MLD lymph and HPV plasma, whereas TG levels were higher in lymph than in plasma. These results indicate that intestinal lymph provides a sensitive readout of intestinal peptide release and potential action, in particular when fat-rich diets are consumed.

Glucagon-like peptide 1 (GLP-1)

“…An exception is glicentin and its cleavage product oxyntomodulin, the concentrations of which need to be combined to match the amount of secreted GLP-1 [41,53]. Meal-induced GLP-1 secretion has been demonstrated in numerous species including mice [227], rats [[228], [229], [230], [231], [232]], dogs [[233], [234], [235]] and humans [[236], [237], [238], [239]]. An important consideration when analyzing meal-induced GLP-1 secretion is whether GLP-1 was measured in systemic or portal vein blood, whether the samples were taken in relation to oral meals or rather to intragastric infusion of liquid (or semiliquid) meals, and whether total or active GLP-1 was measured.…”

Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats

“…The rats were trained to complete this TM within 10 min. Time point “0 min” was marked as soon as the rat started to eat and 60 μL of lymph was sampled at time points 25–29 min and 43–47 min as described earlier [21]. The lymph of both time points was pooled.…”

Actions of glucagon‐like peptide‐1 receptor ligands in the gut

“…It has been speculated that the lymph drainage of the intestine might serve as a route for delivery of GLP‐1 to the circulation (Lu et al, 2012), but the lymph flow is very limited; there may be species differences, and the amounts delivered to the blood stream are probably very small (Hansen et al, 2015; Jejelava et al, 2018).…”