Search

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., (© 2019 Wiley Periodicals, Inc.)

Amino acid mixtures (AAM) are protein substitutes used for phenylketonuria treatment, but their metabolic effects have not been well characterized. The objective of this study was to compare the acute glycemic response to free amino acids (free AA) from AAM with the response to intact protein (iProtein). Male Wistar rats (n = 14) were administered by gavage a bolus of free AA (n = 7) or iProtein as albumin (n = 7) containing equivalent amounts of nitrogen. Blood glucose and insulin levels were measured at baseline and 15, 30, 60 and 120 minutes later, when gut GLP-1 content and pancreatic insulin, GLP-1 receptor and Ki67 expression were quantified at 120 minutes time point. After AAM, glucose area under the curve (free AA vs iProtein; P < 0.01), serum insulin levels at 120 minutes (free AA vs iProtein; P < 0.05), colon GLP-1 content (free AA vs iProtein; P < 0.01), pancreatic GLP-1 receptor (free AA vs iProtein; P < 0.01) and insulin expression (free AA vs iProtein; p < 0.01) were significantly lower as compared with iProtein. AAM increased Ki67 expression in pancreatic islets (free AA vs iProtein; P < 0.05). In conclusion, this study demonstrated that acute response to AAM differs from iProtein and is characterized by a lower glucose excursion, along with a decrease in gut GLP-1 and pancreatic GLP-1 receptor and insulin. This data suggests the modulation of glycemia by free AA is mediated by the incretin axis., (© 2019 Wiley Periodicals, Inc.)

As incretins are known to play an important role in type 2 diabetics (T2D) improvement observed after Roux-en-Y gastric bypass (RYGB), our aim was to assess whether increasing the length of RYGB biliopancreatic limb in T2D would modify the incretin staining cell density found after the gastric outlet. Small intestine biopsies (n = 38) were harvested during RYGB at two different distances from the duodenal angle; either 60-90 cm (n = 28), from non-diabetic (n = 18) patients, and T2D (n = 10), or 200 cm (n = 10) from T2D. GIP and GLP-1 staining cells were identified by immunohistochemistry and GLP-1/GIP co-staining cells by immunofluorescence. Incretin staining cell density at the proximal small intestine of T2D and non-diabetic individuals was similar. At 200 cm, T2D patients depicted a significantly lower GIP staining cell density (0.181 ± 0.016 vs 0.266 ± 0.033, P = 0.038) with a similar GLP-1 staining cell density when compared to the proximal gut. GIP/GLP-1 co-staining cells was similar in all studied groups. In T2D patients, the incretin staining cells density in the distal intestine is significantly different from the proximal gut. Thus, a longer RYGB biliopancreatic limb produces a distinctive incretin cell pattern at the gastro-enteric anastomosis that can result in different endocrine profiles., (© 2018 Wiley Periodicals, Inc.)