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The Effects Of Liraglutide On Diabetic Rat Intestinal Flora And Its Metabolites

Posted on:2016-10-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:L W PaFull Text:PDF
GTID:1224330461976995Subject:Clinical Medicine
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BackgroundDiabetes mellitus is a metabolic disease, and hyperglycemia is the main feature. In 2004 China has became the second largest country with diabetic patient in the world, comes right after India, with about 40 million patients, it is more than the United States and Europe combined. Most diabetic patietnts in our country are with type 2 diabetes, and the percentage of type 2 diabetic patients is 90% or more of the total number. GLP-1 receptor agonist is a new type of anti-diabetes drug, and the secretion of GLP-1 is related to the intestinal flora. The intestinal flora has become a hot topic in the research area, it has been confirmed that intestinal flora is related to a variety of metabolic abnormalities, including obesity and diabetes. Many studies have indicated that diabetes, intestinal flora, GLP-1, short chain fatty acids and dietary fiber are closely related, but the mechanism and causal linksamongthemare not yet fully understood.Objective1. To study the influence of liraglutide to the intestinal flora diversity in diabetic rats;2. To study the effects of liraglutide on short chain fatty acids in feces of diabetic rats;3. To study the possible links among blood glucose, body weight, intestinal microflora and GLP-1 analogs in diabetic rats.Method1.8 week old male SD rats were fed with high fat diet, after 4 weeks they were injectedwith alloxan to cause beta cell damage, select the ratswitha random blood glucose greater than 16.7mmol/L, then randomly divided into four groups along with a control group of 10 healthy rats.2. Rats were divided into control group, model group, low dose group and high dose group, last two groups were treated with liraglutide, while the other two groups were given NS as a placebo. Blood glucose level and body weight were monitored weekly;3. OGTT test was taken after 10 weeks of glp-1 treatment;4.16th weeks anesthesia, leaving the specimen and the execution;5. Levels of short chain fatty acids in feces of rats were tested by gas chromatography;6.16s-rDNA MiSeq method were done to test the intestinal flora in rats.Results1. Liraglutide can in some extent influence the abundance of intestinal flora and in diabetic rats using liraglutid, the abundance of intestinal flora were further reduced.2. Liraglutide increased the content of feces short chain fatty acids in diabetic rats;3. The relative abundance of a glycopeptides resistancing bacteria with the scientific name of Ruminococcus gauvreauii were found increased in the diabetic non treated group, compared with the control group, low dose group and high dose group there were significant differences.ConclusionsLiraglutide and diabetic rat intestinal bacteria abundance were negative correlation, while metabolic products of intestinal flora (short chain fatty acids) were positively correlated with liraglutide. This result may be caused by the effect of liraglutide on gastrointestinal functions. A glycopeptide resistant bacteria, Ruminococcus gauvreauii, in alloxan induced diabetic rat model was increased, and was lowered in the groups using liraglutide, it was not detected in the normal rats in the control group, perhaps it is the result of some functions of GLP-1.
Keywords/Search Tags:GLP-1, diabetes, intestinal flora, short chain fatty acids
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