Ingested glucose powerfully stimulates the secretion of appetite‐ and metabolism‐regulating peptide hormones from the gut – including glucagon‐like peptide‐1 (GLP‐1), neurotensin (NT), and polypeptide YY (PYY). However, the regional origin of these secretions after glucose stimulation is not well characterized, and it remains uncertain how their secretion is related to glucose absorption. We isolated and perfused either the upper (USI) or the lower (LSI) small intestine or the colon from rats and investigated concomitant glucose absorption and secretory profiles of GLP‐1, NT, and PYY. In the USI and LSI luminal glucose (20%, w/v) increased GLP‐1 and NT secretion five to eightfold compared to basal secretion. Compared to the USI, basal and stimulated GLP‐1 secretion from the colon was 8–10 times lower and no NT secretion was detected. Luminal glucose stimulated secretion of PYY four to fivefold from the LSI and from the USI and colon, but the responses in the USI and colon were 5‐ to 15‐fold lower than in the LSI. Glucose was absorbed to a comparable extent in the USI and LSI by mechanisms that partly depended on both SGLT1 and GLUT2 activity, whereas the absorption in the colon was 80–90% lower. The absorption rates were, however, similar when adjusted for segmental length. Glucose absorption rates and NT, PYY and in particular GLP‐1 secretion were strongly correlated (P < 0.05). Our results indicate that the rate of secretion of GLP‐1, NT, and PYY in response to glucose, regardless of the involved molecular machinery, is predominantly regulated by the rate of glucose absorption.

Glucose stimulates the secretion of the incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). It is debated whether the sweet taste receptor (STR) triggers this secretion. We investigated the role of STR activation for glucose-stimulated incretin secretion from an isolated perfused rat small intestine and whether selective STR activation by artificial sweeteners stimulates secretion. Intra-luminal administration of the STR agonists, acesulfame K (3.85% w/v), but not sucralose (1.25% w/v) and stevioside (2.5% w/v), stimulated GLP-1 secretion (acesulfame K: 31 ± 3 pmol/L vs. 21 ± 2 pmol/L, p < 0.05, n = 6). In contrast, intra-arterial administration of sucralose (10 mM) and stevioside (10 mM), but not acesulfame K, stimulated GLP-1 secretion (sucralose: 51 ± 6 pmol/L vs. 34 ± 4 pmol/L, p < 0.05; stevioside: 54 ± 6 pmol/L vs. 32 ± 2 pmol/L, p < 0.05, n = 6), while 0.1 mM and 1 mM sucralose did not affect the secretion. Luminal glucose (20% w/v) doubled GLP-1 and GIP secretion, but basolateral STR inhibition by gurmarin (2.5 µg/mL) or the inhibition of the transient receptor potential cation channel 5 (TRPM5) by triphenylphosphine oxide (TPPO) (100 µM) did not attenuate the responses. In conclusion, STR activation does not drive GIP/GLP-1 secretion itself, nor does it have a role for glucose-stimulated GLP-1 or GIP secretion.

Aims Previous results indicate that nanomolar concentrations of abscisic acid (ABA) stimulate insulin release from β‐pancreatic cells in vitro and that oral ABA at 50 mg/kg increases plasma GLP‐1 in the fasted rat. The aim of this study was to test the effect of ABA on the perfused rat pancreas and intestine, to verify the insulin‐ and incretin‐releasing actions of ABA in controlled physiological models. Materials and methods Rat pancreas and small intestine were perfused with solutions containing ABA at high‐micromolar concentrations, or control secretagogues. Insulin and GLP‐1 concentrations in the venous effluent were analysed by radioimmunoassay, and ABA levels were determined by ELISA. Results High micromolar concentrations of ABA induced GLP‐1 secretion from the proximal half of the small intestine and insulin secretion from pancreas. GLP‐1 stimulated ABA secretion from pancreas in a biphasic manner. Notably, a positive correlation was found between the ABA area under the curve (AUC) and the insulin AUC upon GLP‐1 administration. Conclusion Our results indicate the existence of a cross talk between GLP‐1 and ABA, whereby ABA stimulates GLP‐1 secretion, and vice versa. Release of ABA could be considered as a new promising molecule in the strategy of type 2 diabetes treatment and as a new endogenous hormone in the regulation of glycaemia.