Diet-induced obesity enhances postprandial glucagon-like peptide-1 secretion in Wistar rats, but not in diabetic Goto-Kakizaki rats

2020 ◽  
pp. 1-13
Author(s):  
Jukkrapong Pinyo ◽  
Hiroshi Hara ◽  
Tohru Hira
Keyword(s):  
Wistar Rats ◽  
Control Diet ◽  
Postprandial Glucose ◽  
Diabetic Rats ◽  
Gk Rats ◽  
Obesity And Diabetes ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulin Responses

Abstract Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.

scholarly journals Resistant starch and arabinoxylan augment SCFA absorption, but affect postprandial glucose and insulin responses differently

2014 ◽  
Vol 111 (9) ◽  
pp. 1564-1576 ◽  
Author(s):  
Anne Krog Ingerslev ◽  
Peter Kappel Theil ◽  
Mette Skou Hedemann ◽  
Helle Nygaard Lærke ◽  
Knud Erik Bach Knudsen
Keyword(s):  
Resistant Starch ◽  
Control Diet ◽  
Postprandial Glucose ◽  
Relative Increase ◽  
Hepatic Veins ◽  
Colonic Fermentation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulinotropic Peptide ◽  
Insulin Responses

The effects of increased colonic fermentation of dietary fibres (DF) on the net portal flux (NPF) of carbohydrate-derived metabolites (glucose, SCFA and, especially, butyrate), hormones (insulin, C-peptide, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide) and NEFA were studied in a healthy catheterised pig model. A total of six pigs weighing 59 (sem1·6) kg were fitted with catheters in the mesenteric artery and in the portal and hepatic veins, and a flow probe around the portal vein, and included in a double 3 × 3 cross-over design with three daily feedings (at 09.00, 14.00 and 19.00 hours). Fasting and 5 h postprandial blood samples were collected after 7 d adaptation to each diet. The pigs were fed a low-DF Western-style control diet (WSD) and two high-DF diets (an arabinoxylan-enriched diet (AXD) and a resistant starch-enriched diet (RSD)). The NPF of insulin was lower (P= 0·04) in AXD-fed pigs (4·6 nmol/h) than in RSD-fed pigs (10·5 nmol/h), despite the lowest NPF of glucose being observed in RSD-fed pigs (203 mmol/h,P= 0·02). The NPF of total SCFA, acetate, propionate and butyrate were high, intermediate and low (P< 0·01) in AXD-, RSD- and WSD-fed pigs, respectively, with the largest relative increase being observed for butyrate in response to arabinoxylan supplementation. In conclusion, the RSD and AXD had different effects on the NPF of insulin and glucose, suggesting different impacts of arabinoxylan and resistant starch on human health.

scholarly journals Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Suppress Voluntary Alcohol Intake in Male Wistar Rats

2020 ◽  
Vol 14 ◽  
Author(s):  
Vincent N. Marty ◽  
Mehdi Farokhnia ◽  
Joseph J. Munier ◽  
Yatendra Mulpuri ◽  
Lorenzo Leggio ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Alcohol Intake ◽  
Ethanol Intake ◽  
Addictive Behaviors ◽  
Gut Hormone ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Alcohol Seeking

Alcohol use disorder (AUD) is a chronic relapsing condition characterized by compulsive alcohol-seeking behaviors, with serious detrimental health consequences. Despite high prevalence and societal burden, available approved medications to treat AUD are limited in number and efficacy, highlighting a critical need for more and novel pharmacotherapies. Glucagon-like peptide-1 (GLP-1) is a gut hormone and neuropeptide involved in the regulation of food intake and glucose metabolism via GLP-1 receptors (GLP-1Rs). GLP-1 analogs are approved for clinical use for diabetes and obesity. Recently, the GLP-1 system has been shown to play a role in the neurobiology of addictive behaviors, including alcohol seeking and consumption. Here we investigated the effects of different pharmacological manipulations of the GLP-1 system on escalated alcohol intake and preference in male Wistar rats exposed to intermittent access 2-bottle choice of 10% ethanol or water. Administration of AR231453 and APD668, two different agonists of G-protein receptor 119, whose activation increases GLP-1 release from intestinal L-cells, did not affect voluntary ethanol intake. By contrast, injections of either liraglutide or semaglutide, two long-acting GLP-1 analogs, potently decreased ethanol intake. These effects, however, were transient, lasting no longer than 48 h. Semaglutide, but not liraglutide, also reduced ethanol preference on the day of injection. As expected, both analogs induced a reduction in body weight. Co-administration of exendin 9-39, a GLP-1R antagonist, did not prevent liraglutide- or semaglutide-induced effects in this study. Injection of exendin 9-39 alone, or blockade of dipeptidyl peptidase-4, an enzyme responsible for GLP-1 degradation, via injection of sitagliptin, did not affect ethanol intake or preference. Our findings suggest that among medications targeting the GLP-1 system, GLP-1 analogs may represent novel and promising pharmacological tools for AUD treatment.

scholarly journals Nutrient-driven incretin secretion into intestinal lymph is different between diabetic Goto-Kakizaki rats and Wistar rats

2009 ◽  
Vol 296 (2) ◽  
pp. G168-G174 ◽  
Author(s):  
Tammy L. Kindel ◽  
Qing Yang ◽  
Stephanie M. Yoder ◽  
Patrick Tso
Keyword(s):  
Wistar Rats ◽  
Area Under The Curve ◽  
Gastric Inhibitory Polypeptide ◽  
Wistar Rat ◽  
Postprandial Glucose ◽  
Mixed Meal ◽  
Gk Rats ◽  
Lymphatic Duct ◽  
Incretin Secretion ◽  
Glucagon Like Peptide 1

The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) augment postprandial glucose-mediated insulin release from pancreatic β-cells. The Goto-Kakizaki (GK) rat is a widely used, lean rodent model of Type 2 diabetes; however, little is known regarding the incretin secretion profile to different nutrients in these rats. We have recently shown that lymph is a sensitive medium to measure incretin secretion in rodents and probably the preferred compartment for GLP-1 monitoring. To characterize the meal-induced incretin profile, we compared lymphatic incretin concentrations in the GK and Wistar rat after enteral macronutrient administration. After cannulation of the major mesenteric lymphatic duct and duodenum, each animal received an intraduodenal bolus of either a fat emulsion, dextrin, a mixed meal, or saline. Lymph was collected for 3 h and analyzed for triglyceride, glucose, GLP-1, and GIP content. There was no statistical difference in GIP or GLP-1 secretion after a lipid bolus between GK and Wistar rats. Dextrin and a mixed meal both increased incretin concentration area under the curve, however, significantly less in GK rats compared with Wistar rats (dextrin GIP: 707 ± 106 vs. 1,373 ± 114 pg·ml−1·h, respectively, P < 0.001; dextrin GLP-1: 82.7 ± 24.3 vs. 208.3 ± 26.3 pM/h, respectively, P = 0.001). After administration of a carbohydrate-containing meal, GK rats were unable to mount as robust a response of both GIP and GLP-1 compared with Wistar rats, a phenomenon not seen after a lipid meal. We propose a similar, glucose-mediated incretin secretion pathway defect of both K and L cells in GK rats.

scholarly journals Involvement of endogenous glucagon-like peptide-1(7–36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats

2005 ◽  
Vol 185 (3) ◽  
pp. 457-465 ◽  
Author(s):  
Patrice D Cani ◽  
Catherine A Daubioul ◽  
Brigitte Reusens ◽  
Claude Remacle ◽  
Grégory Catillon ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Food Restriction ◽  
Tolerance Test ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Standard Diet ◽  
Mrna Levels ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

We have evaluated the influence of oligofructose (OFS), a fermentable dietary fibre, on glucose homeostasis, insulin production and intestinal glucagon-like peptide-1 (GLP-1) in streptozotocin-treated diabetic rats. Male Wistar rats received either i.v. streptozotocin (STZ; 40 mg/kg) or vehicle (CT); one week later, they were fed for 6 weeks with either the standard diet (STZ-CT), or with a diet containing 10% oligofructose (STZ-OFS); both diets were available ad libitum. In a second set of experiments (duration 4 weeks), a supplemental group of food-restricted rats (STZ-Res) receiving a similar intake as CT rats, was added. OFS improved glucose tolerance and reduced food intake as compared with STZ-CT rats in both the post-prandial state and after an oral glucose tolerance test. After 6 weeks, portal and pancreatic insulin concentrations were doubled in STZ-OFS rats. Food restriction improved these parameters when compared with STZ-CT rats, but to a lesser extent than in the STZ-OFS group. We have shown that OFS treatment increased portal and colonic GLP-1(7–36) amide levels and doubled colonic proglucagon and prohormone convertase 1 mRNA levels; both OFS and food restriction lowered ileal GLP-1(7–36) amide levels as compared with levels in STZ-CT rats. We propose that OFS, through its fermentation in the colon, promotes the expression and secretion of colonic peptides, namely GLP-1(7–36) amide, with beneficial consequences on glycaemia, insulin secretion and hyperphagia in diabetic rats.

Effects of glucagon-like peptide-1-(7–36)-amide on pancreatic islet and intestinal blood perfusion in Wistar rats and diabetic GK rats

2007 ◽  
Vol 112 (6) ◽  
pp. 345-351 ◽  
Author(s):  
Annika M. Svensson ◽  
Claes-Göran Östenson ◽  
Suad Efendic ◽  
Leif Jansson
Keyword(s):  
Blood Flow ◽  
Pancreatic Islet ◽  
Wistar Rats ◽  
Blood Perfusion ◽  
Glucose Administration ◽  
Gk Rats ◽  
Islet Blood Flow ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Pre Treatment

The aim of the present study was to evaluate the effects of GLP-1 [glucagon-like peptide-1-(7–36)-amide] on total pancreatic, islet and intestinal blood perfusion in spontaneously hyperglycaemic GK rats and normal Wistar rats using a microsphere technique. GK rats had hyperglycaemia and increased pancreatic and islet blood flow. Blood glucose concentrations were not affected when measured shortly (8 min) after GLP-1 administration in either GK or Wistar rats. GLP-1 had no effects on baseline pancreatic or islet blood flow in Wistar rats, but did prevent the blood flow increase normally seen following glucose administration to these animals. In GK rats, administration of GLP-1 decreased both pancreatic and islet blood flow. Glucose administration to the GK rats decreased pancreatic and islet blood flow. This decrease was not affected by pre-treatment with GLP-1. We conclude that administration of GLP-1 leads to a decrease in the augmented blood flow seen in islets of diabetic GK rats. The GLP-1-induced action on islet blood perfusion may modulate output of islet hormones and contribute to the antidiabetogenic effects of the drug in Type 2 diabetes (non-insulin-dependent diabetes).

scholarly journals Liraglutide Preserves Intracellular Calcium Handling in Isolated Murine Myocytes Exposed to Oxidative Stress

2017 ◽  
pp. 889-895 ◽  
Author(s):  
S. PALEE ◽  
S. C. CHATTIPAKORN ◽  
N. CHATTIPAKORN
Keyword(s):  
Oxidative Stress ◽  
Decay Rate ◽  
Intracellular Calcium ◽  
Wistar Rats ◽  
Calcium Handling ◽  
Isolated Cardiomyocytes ◽  
Before And After ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

In ischemic/reperfusion (I/R) injured hearts, severe oxidative stress occurs and is associated with intracellular calcium (Ca2+) overload. Glucagon-Like Peptide-1 (GLP-1) analogues have been shown to exert cardioprotection in I/R heart. However, there is little information regarding the effects of GLP-1 analogue on the intracellular Ca2+ regulation in the presence of oxidative stress. Therefore, we investigated the effects of GLP-1 analogue, (liraglutide, 10 µM) applied before or after hydrogen peroxide (H2O2, 50 µM) treatment on intracellular Ca2+ regulation in isolated cardiomyocytes. We hypothesized that liraglutide can attenuate intracellular Ca2+ overload in cardiomyocytes under H2O2-induced cardiomyocyte injury. Cardiomyocytes were isolated from the hearts of male Wistar rats. Isolated cardiomyocytes were loaded with Fura-2/AM and fluorescence intensity was recorded. Intracellular Ca2+ transient decay rate, intracellular Ca2+ transient amplitude and intracellular diastolic Ca2+ levels were recorded before and after treatment with liraglutide. In H2O2 induced severe oxidative stressed cardiomyocytes (which mimic cardiac I/R) injury, liraglutide given prior to or after H2O2 administration effectively increased both intracellular Ca2+ transient amplitude and intracellular Ca2+ transient decay rate, without altering the intracellular diastolic Ca2+ level. Liraglutide attenuated intracellular Ca2+ overload in H2O2-induced cardiomyocyte injury and may be responsible for cardioprotection during cardiac I/R injury by preserving physiological levels of calcium handling during the systolic and diastolic phases of myocyte activation.

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.

Effect of Glucagon-Like Peptide-1(7–36) and Exendin-4 on the Vascular Reactivity in Streptozotocin/Nicotinamide-Induced Diabetic Rats

Pharmacology ◽  
2005 ◽  
Vol 74 (3) ◽  
pp. 119-126 ◽  
Author(s):  
Sibel Özyazgan ◽  
Nilüfer Kutluata ◽  
Selim Afşar ◽  
Şule Beyhan Özdaş ◽  
Ahmet Gökhan Akkan
Keyword(s):  
Vascular Reactivity ◽  
Diabetic Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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