scholarly journals The Role of the Bacterial Muramyl Dipeptide in the Regulation of GLP-1 and Glycemia

2020 ◽  
Vol 21 (15) ◽  
pp. 5252
Author(s):  
Laura Williams ◽  
Amal Alshehri ◽  
Bianca Robichaud ◽  
Alison Cudmore ◽  
Jeffrey Gagnon
Keyword(s):  
Glucose Tolerance ◽  
Muramyl Dipeptide ◽  
Gut Hormones ◽  
Oral Glucose ◽  
L Cells ◽  
Nucleotide Oligomerization ◽  
Mouse Intestine ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The host’s intestinal microbiota contributes to endocrine and metabolic responses, but a dysbiosis in this environment can lead to obesity and insulin resistance. Recent work has demonstrated a role for microbial metabolites in the regulation of gut hormones, including the metabolic hormone, glucagon-like peptide-1 (GLP-1). Muramyl dipeptide (MDP) is a bacterial cell wall component which has been shown to improve insulin sensitivity and glucose tolerance in diet-induced obese mice by acting through the nucleotide oligomerization domain 2 (NOD2) receptor. The purpose of this study was to understand the effects of MDP on GLP-1 secretion and glucose regulation. We hypothesized that MDP enhances glucose tolerance by inducing intestinal GLP-1 secretion through NOD2 activation. First, we observed a significant increase in GLP-1 secretion when murine and human L-cells were treated with a fatty acid MDP derivative (L18-MDP). Importantly, we demonstrated the expression of the NOD2 receptor in mouse intestine and in L-cells. In mice, two intraperitoneal injections of MDP (5 mg/kg body weight) caused a significant increase in fasting total GLP-1 in chow-fed mice, however this did not lead to an improvement in oral glucose tolerance. When mice were exposed to a high-fat diet, they eventually lost this MDP-induced GLP-1 release. Finally, we demonstrated in L-cells that hyperglycemic conditions reduce the mRNA expression of NOD2 and GLP-1. Together these findings suggest MDP may play a role in enhancing GLP-1 during normal glycemic conditions but loses its ability to do so in hyperglycemia.

scholarly journals TNF signaling impacts glucagon-like peptide-1 expression and secretion

2018 ◽  
Vol 61 (4) ◽  
pp. 153-161 ◽  
Author(s):  
Sufang Chen ◽  
Wei Wei ◽  
Minjie Chen ◽  
Xiaobo Qin ◽  
Lianglin Qiu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Deficient Mice

Numerous studies have implicated tumor necrosis factor α (TNFα) in the pathogenesis of type 2 diabetes. However, the role of its primary receptor, TNF receptor 1 (TNFR1), in homeostatic regulation of glucose metabolism is still controversial. In addition to TNFα, lymphotoxin α (LTα) binds to and activates TNFR1. Thus, TNFα and LTα together are known as TNF. To delineate the role of TNF signaling in glucose homeostasis, the present study ascertained how TNF signaling deficiency affects major regulatory components of glucose homeostasis. To this end, normal diet-fed male TNFR1-deficient mice (TNFR1−/−), TNFα/LTα/LTβ triple-deficient mice (TNF/LT∆3) and their littermate controls were subjected to intraperitoneal glucose tolerance test, insulin tolerance test and oral glucose tolerance test. The present results showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had comparable body weight, tolerance to intraperitoneal glucose and sensitivity to insulin. However, their tolerance to oral glucose was significantly increased. Additionally, glucose-induced insulin secretion assessments revealed that TNFR1 or TNF/LT deficiency significantly increased oral but not intraperitoneal glucose-induced insulin secretion. Consistently, qPCR and immunohistochemistry analyses showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had significantly increased ileal expression of glucagon-like peptide-1 (GLP-1), one of the primary incretins. Their oral glucose-induced secretion of GLP-1 was also significantly increased. These data collectively suggest that physiological TNF signaling regulates glucose metabolism primarily through effects on GLP-1 expression and secretion and subsequently insulin secretion.

scholarly journals MON-666 Glucokinase Within the Hypothalamic Paraventricular Nucleus Is Important in GLP-1 Release

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Risheka Ratnasabapathy
Keyword(s):  
Glucose Tolerance ◽  
Paraventricular Nucleus ◽  
Glucose Sensing ◽  
Hypothalamic Paraventricular Nucleus ◽  
Oral Glucose ◽  
Insulin Synthesis ◽  
Glucose Intake ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract When glucose is taken orally more insulin is secreted than when glucose is injected directly into the bloodstream. This is known as the incretin effect. Glucagon like peptide 1 (GLP-1) is one of the hormones responsible for this effect. GLP-1 is released from enteroendocrine L-cells in the gut in response to oral glucose intake. GLP-1 increases insulin synthesis and secretion. Release of GLP-1 is thought to be solely dependent upon gastrointestinal tract mechanisms. Here we identify a brain mechanism via the hypothalamic paraventricular nucleus (PVN) which is important in the release of GLP-1 in response to oral glucose. The role of the paraventricular nucleus in glucose homeostasis was previously unknown. We found that a glucokinase dependent glucose sensing mechanism in the PVN works in conjunction with the gut to regulate GLP-1 release. We show that increasing expression of GK (sense GK, sGK) into the PVN improves glucose tolerance (15 minutes glucose: GFP: 8.93±0.27mmol/L, n=11; sGK: 7.72±0.22mmol/L, n=12; p<0.01 and 15 minutes insulin GFP: 2.84±0.14mmol/L, n=11; sGK: 3.73±0.27mmol/L, n=12; p<0.01) and increases GLP-1 release in response to oral glucose (GFP: 6.16±0.18mmol/L, n=11; sGK: 6.90±0.26mmol/L, n=12; p<0.01). On the contrary decreasing expression of GK (antisense GK, asGK) in the PVN worsens glucose tolerance (30 minutes glucose: GFP: 8.22±0.28mmol/L; asGK: 9.46±0.24mmol/L, n=8; p<0.01 and 15 minutes insulin: GFP: 4.07±0.37mmol/L; asGK: 2.25±0.17mmol/L, n=8; p<0.001) and blunts (GLP-1 release 30 minutes GLP-1: GFP: 6.93±0.25pMol/L, n=8; p<0.01 asGK: 5.47±0.13pMol/L, n=8; p<0.001). Our results demonstrate that glucosensitive GK neurones in the PVN, are important to the response to oral glucose and the subsequent release of GLP-1.

Reduced gastric inhibitory polypeptide but normal glucagon-like peptide 1 response to oral glucose in postmenopausal women with impaired glucose tolerance

1997 ◽  
pp. 127-131 ◽  
Author(s):  
B Ahren ◽  
H Larsson ◽  
JJ Holst
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Postmenopausal Women ◽  
Plasma Levels ◽  
Insulin Response ◽  
Gastric Inhibitory Polypeptide ◽  
Oral Glucose ◽  
Glucose Ingestion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

OBJECTIVE: The gastrointestinal hormones, gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are both released from the gut after oral glucose ingestion and stimulate insulin secretion. This study examined the release of these hormones in subjects with impaired glucose tolerance (IGT), which precedes the development of non-insulin-dependent diabetes. DESIGN AND METHODS: Six postmenopausal women with IGT, aged 59 years, underwent a 75 g oral glucose tolerance test and plasma levels of GIP and GLP-1 were determined regularly during the following 2 h. The results were compared with those in seven age- and weight-matched women with normal glucose tolerance (NGT). RESULTS: Basal plasma levels of GIP and GLP-1 were not different between the groups. In response to the oral glucose ingestion, plasma levels of both GIP and GLP-1 increased in both groups. The plasma GIP increase after glucose ingestion was, however, reduced in women with IGT. Thus, the GIP response as determined as the area under the curve for the 60 min after oral glucose was 34.8 +/- 3.2 pmol/l per min in women with IGT versus 56.4 +/- 7.8 pmol/l per min in those with NGT (P = 0.021). In contrast, the GLP-1 response to oral glucose was not different between the groups. By definition, the glucose response to oral glucose was markedly increased in women with IGT, and the insulin response during the second hour after glucose ingestion was exaggerated. CONCLUSIONS: The GIP response to oral glucose is impaired in postmenopausal women with IGT, whereas the plasma GLP-1 response is not affected.

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.

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