scholarly journals Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats

2015 ◽  
Vol 113 (9) ◽  
pp. 1477-1488 ◽  
Author(s):  
Shingo Nakajima ◽  
Tohru Hira ◽  
Hiroshi Hara
Keyword(s):  
Gastric Emptying ◽  
Glucose Intolerance ◽  
Control Group ◽  
Mrna Levels ◽  
High Fat ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Meal Ingestion ◽  
High Sucrose

Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity.

scholarly journals Glucagon-Like Peptide-1 (GLP-1) Reduces Mortality and Improves Lung Function in a Model of Experimental Obstructive Lung Disease in Female Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4503-4511 ◽  
Author(s):  
Niels-Erik Viby ◽  
Marie S. Isidor ◽  
Katrine B. Buggeskov ◽  
Steen S. Poulsen ◽  
Jacob B. Hansen ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Whole Body ◽  
Control Group ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Female Mice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P < .001). Survival proportions were significantly increased in GLP-1R agonist-treated mice (P < .01). SFTPB and SFTPA were down-regulated and the expression of inflammatory cytokines were increased in mice with obstructive lung disease, but levels were largely unaffected by GLP-1R agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

MiR-425-5p Regulates Glucagon-like Peptide-1 Production and Affects Blood Glucose Levels in High-fat Diet-fed Mice

2021 ◽  
Author(s):  
Lirui Wei ◽  
Xuenan Zhao ◽  
Feng Guo ◽  
Fengjiao Huang ◽  
Yanyan Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Protein Level ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Tolerance Test ◽  
Control Group ◽  
High Fat ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract BackgroundIn modern society, obesity has become a global problem with resulting in metabolic disorders and poses high risk for type 2 diabetes mellitus (T2DM). The glucagon-like peptide-1 (GLP-1) has been taken as an effective drug for the therapy of T2DM and obesity. In the present study, the regulatory roles and molecular mechanisms of miR-425-5p in GLP-1 secretion in high-fat diet (HFD)-induced diabetic mice were explored. MethodsOral glucose tolerance test and insulin tolerance test were performed to assess glucose metabolism and GLP-1 and LPS levels. Quantitative real time polymerase chain reaction (qRT-PCR) was employed to detect the expression of LPS, GLP-1, GLP-1 receptors, miR-425-5p, phosphatase and tensin homology (PTEN), proglucagon, p65 and β-catenin. Western blot was performed to determine the expression of proglucagon, p65, β-catenin and PTEN. ResultsThe results showed that plasma GLP-1 level was negatively correlated with plasma LPS level in HFD-fed mice, and miR-425-5p expression and LPS level were up-regulated in the ileal fluid compared with control groups. LPS injection boosted miR-425-5p expression in ileum. MiR-425-5p ameliorated glucose intolerance and insulin resistance in HFD-fed mice by increasing GLP-1 secretion. Furthermore, p65 protein level in the cytoplasmic and nuclear in the ileum of HFD-fed mice was increased compared with the control group. MiR-425-5p agomir elevated nuclear β-catenin protein level, but reduced PTEN protein level in HFD-fed mice compared with HFD-fed mice treated with the miR-425-5p antagomir. ConclusionsOur results suggest that miR-425-5p promotes GLP-1 secretion and improves glucose tolerance and insulin resistance in high-fat diet-fed mice.

Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

2004 ◽  
Vol 286 (4) ◽  
pp. E621-E625 ◽  
Author(s):  
Juris J. Meier ◽  
Oliver Goetze ◽  
Jens Anstipp ◽  
Dirk Hagemann ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Repeated Measures ◽  
Venous Blood ◽  
Area Under The Curve ◽  
Gastric Inhibitory Polypeptide ◽  
Time Pattern ◽  
C Peptide ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1 ◽  
Meal Ingestion

The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess “enterogastrone” activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 ± 3.3 yr, body mass index 23.7 ± 2.3 kg/m2) were studied with the intravenous infusion of GIP (2 pmol·kg-1·min-1) or placebo, each administered to the volunteers on separate occasions from -30 to 360 min in the fasting state. At 0 min, a solid test meal (250 kcal containing [13C]sodium octanoate) was served. Gastric emptying was calculated from the 13CO2 exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA and one-way ANOVA. During the infusion, GIP rose to steady-state concentrations of 159 ± 15 pmol/l for total and 34 ± 4 pmol/l for intact GIP ( P < 0.0001). Meal ingestion further increased GIP concentrations in both groups, reaching peak levels of 265 ± 20 and 82 ± 9 pmol/l for total and 67 ± 7 and 31 ± 9 pmol/l for intact GIP during the administration of GIP and placebo, respectively ( P < 0.0001). There were no differences in glucose, insulin, and C-peptide between the experiments with the infusion of GIP or placebo. Gastric half-emptying times were 120 ± 9 and 120 ± 18 min ( P = 1.0, with GIP and placebo, respectively). The time pattern of gastric emptying was similar in the two groups ( P = 0.98). Endogenous GIP secretion, as derived from the incremental area under the curve of plasma GIP concentrations in the placebo experiments, did not correlate to gastric half-emptying times ( r2 = 0.15, P = 0.15 for intact GIP; r2 = 0.21, P = 0.086 for total GIP). We conclude that gastric emptying does not appear to be influenced by GIP. The secretion of GIP after meal ingestion is not suppressed by its exogenous administration. The lack of effect of GIP on gastric emptying underlines the differences between GIP and the second incretin glucagon-like peptide 1.

scholarly journals High-Fat Diet and Palmitate Alter the Rhythmic Secretion of Glucagon-Like Peptide-1 by the Rodent L-cell

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 586-599 ◽  
Author(s):  
Manuel Gil-Lozano ◽  
W. Kelly Wu ◽  
Alexandre Martchenko ◽  
Patricia L. Brubaker
Keyword(s):  
Molecular Clock ◽  
Rhythmic Activity ◽  
Induced Responses ◽  
High Fat ◽  
L Cells ◽  
L Cell ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Impact ◽  
High Sucrose

Abstract Secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is rhythmically regulated by an independent molecular clock. However, the impact of factors known to affect the activity of similar cell-autonomous clocks, such as circulating glucocorticoids and high-fat feeding, on GLP-1 secretory patterns remains to be elucidated. Herein the role of the endogenous corticosterone rhythm on the pattern of GLP-1 and insulin nutrient-induced responses was examined in corticosterone pellet-implanted rats. Moreover, the impact of nutrient excess on the time-dependent secretion of both hormones was assessed in rats fed a high-fat, high-sucrose diet. Finally, the effects of the saturated fatty acid, palmitate, on the L-cell molecular clock and GLP-1 secretion were investigated in vitro using murine GLUTag L-cells. Diurnal variations in GLP-1 and insulin nutrient-induced responses were maintained in animals lacking an endogenous corticosterone rhythm, suggesting that glucocorticoids are not the predominant entrainment factor for L-cell rhythmic activity. In addition to hyperglycemia, hyperinsulinemia, insulin resistance, and disorganization of feeding behavior, high-fat high-sucrose-fed rats showed a total abrogation of the diurnal variation in GLP-1 and insulin nutrient-induced responses, with comparable levels of both hormones at the normal peak (5:00 pm) and trough (5:00 am) of their daily pattern. Finally, palmitate incubation induced profound derangements in the rhythmic expression of circadian oscillators in GLUTag L-cells and severely impaired the secretory activity of these cells. Collectively our findings demonstrate that obesogenic diets disrupt the rhythmic activity of the L-cell, partially through a direct effect of specific nutritional components.

scholarly journals Resistant maltodextrin promotes fasting glucagon-like peptide-1 secretion and production together with glucose tolerance in rats

2015 ◽  
Vol 114 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Tohru Hira ◽  
Asuka Ikee ◽  
Yuka Kishimoto ◽  
Sumiko Kanahori ◽  
Hiroshi Hara
Keyword(s):  
Glucose Tolerance ◽  
Cell Model ◽  
Water Soluble ◽  
Control Group ◽  
Mrna Levels ◽  
Glycaemic Response ◽  
Control Male ◽  
Resistant Maltodextrin ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), which is produced and released from enteroendocrine L cells, plays pivotal roles in postprandial glycaemia. The ingestion of resistant maltodextrin (RMD), a water-soluble non-digestible saccharide, improves the glycaemic response. In the present study, we examined whether the continuous feeding of RMD to rats affected GLP-1 levels and glycaemic control. Male Sprague–Dawley rats (6 weeks of age) were fed an American Institute of Nutrition (AIN)-93G-based diet containing either cellulose (5 %) as a control, RMD (2·5 or 5 %), or fructo-oligosaccharides (FOS, 2·5 or 5 %) for 7 weeks. During the test period, an intraperitoneal glucose tolerance test (IPGTT) was performed after 6 weeks. Fasting GLP-1 levels were significantly higher in the 5 % RMD group than in the control group after 6 weeks. The IPGTT results showed that the glycaemic response was lower in the 5 % RMD group than in the control group. Lower caecal pH, higher caecal tissue and content weights were observed in the RMD and FOS groups. Proglucagon mRNA levels were increased in the caecum and colon of both RMD and FOS groups, whereas caecal GLP-1 content was increased in the 5 % RMD group. In addition, a 1 h RMD exposure induced GLP-1 secretion in an enteroendocrine L-cell model, and single oral administration of RMD increased plasma GLP-1 levels in conscious rats. The present study demonstrates that continuous ingestion of RMD increased GLP-1 secretion and production in normal rats, which could be stimulated by its direct and indirect (enhanced gut fermentation) effects on GLP-1-producing cells, and contribute to improving glucose tolerance.

scholarly journals Enhanced postprandial glucagon-like peptide-1 secretion during obesity development has a protective role against glucose intolerance induction in rats

2019 ◽  
Vol 122 (04) ◽  
pp. 411-422 ◽  
Author(s):  
Jukkrapong Pinyo ◽  
Tohru Hira ◽  
Hiroshi Hara
Keyword(s):  
Glucose Intolerance ◽  
Control Diet ◽  
Insulin Response ◽  
Postprandial Glucose ◽  
Control Group ◽  
Sprague Dawley ◽  
Glycaemic Response ◽  
Continuous Administration ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

AbstractGlucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glycaemic response by enhancing insulin secretion. We previously demonstrated that the postprandial GLP-1 response was enhanced during the development of diet-induced obesity in rats. However, the physiological relevance of the enhanced GLP-1 response remained unclear. We aimed to determine the role of endogenous GLP-1 during obesity development. Male Sprague–Dawley rats were given either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose, weight basis) diet with or without continuous administration of the GLP-1 receptor antagonist, exendin (9–39) (Ex9, 100 µg/d), for 5 weeks. Meal tolerance tests (MTT) were performed to assess postprandial glucose, insulin and GLP-1 responses to a liquid diet administration (15 kcal (63 kJ)/10 ml per kg body weight) every 2 weeks. The AUC of postprandial glucose in the HFS group was similar to the control group in both MTT (P = 0·9665 and P = 0·3475, respectively), whereas AUC of postprandial GLP-1 (after 4 weeks,P = 0·0457) and of insulin (after 2 and 4 weeks, P = 0·0486 and P = 0·0110) was higher in the HFS group compared with the control group. In the Ex9 group, AUC of postprandial glucose (P = 0·0297 and P = 0·0486) was higher along with a lower insulin response compared with the HFS group (P = 0·0564 and P = 0·0281). These results suggest that enhancement of the postprandial GLP-1 response during obesity development has a role in maintaining a normal postprandial glycaemic response. Hence, enhancing endogenous GLP-1 secretion by certain materials could be a potential target for prevention of glucose intolerance.

Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: Relationship to glycemia*

2010 ◽  
Vol 38 (5) ◽  
pp. 1261-1269 ◽  
Author(s):  
Adam M. Deane ◽  
Marianne J. Chapman ◽  
Robert J. L. Fraser ◽  
Matthew J. Summers ◽  
Antony V. Zaknic ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Critically Ill ◽  
Glucose Absorption ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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