Protective effect of liraglutide on the myocardium of type 2 diabetic rats by inhibiting polyadenosine diphosphate-ribose polymerase-1

BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.

Anti-diabetic Activity of Zhenqing Recipe and Ligustri Lucidi Fructus in Type 2 Diabetic Rats

Objective To investigate the influence of Zhenqing Recipe(ZQR)and Ligustri Lucidi Fructus(LLF)on diabetic rats and its possible mechanism.Methods The model of type 2 diabetic rats was established by feeding a high-sucrose-high-fat diet and injecting a low dose of Streptozotocin in Wistar rats.The model rats were randomly divided into three groups:diabetic model,ZQR-treated,and LLF-treated groups for 8-weeks treatment.The normal Wistar rats were as a normal control group.Results The level of fasting blood glucose in ZQR and LLF groups was decreased compared with model group(P<0.01,0.05,respectively).Both ZQR and LLF markedly reduced serum triglycerides(P<0.01,0.05,respectively),and increased the insulin sensitivity index(P<0.05).Histopathology revealed that ZQR and LLF reduced pancreatic damage.Immunohistochemistry evaluation showed that the percentage of insulin positive cells in pancreatic island was higher than model group(P<0.01,0.05,respectively).The mRNA and protein expression of SREBP-1c in pancreas were significantly decreased in ZQR and FLL group(P<0.01).Conclusion ZQR has therapeutic effect on type 2 diabetes,it ameliorates the histopathological changes of pancreas,protectsβcells,improves insulin resistance,and attenuates the expression of SREBP-1c.This study also provides the anti-diabetic evidence of FLL even its effects are weaker than ZQR.

Pterostilbene Ameliorates Glycemic Control,Dyslipidemia and Liver Injury in Type 2 Diabetes Rats

Type 2 diabetes mellitus(T2DM)is typified by the increment of chronic blood glucose levels that is caused by an absolute and/or a relative deficiency of insulin,accounts for 90%of diabetes and causes a range of complications[1].

Effects of gliclazide on myocardial protection of isolated type 2 diabetic rat heart afforded by ischemic preconditioning

The myocardial protection afforded by ischernic preconditioning （IPC） can alleviate ischemi- a-repel-fusion injury in normal rat heart. However, this myocardial protection is seldom studied in the type 2 diabetic rat with myocardial ischemia disease. In this study, we aimed to evaluate the effects of ATP-sensitive potassium channels （KATP channels） on IPC in the isolated type 2 diabetic rat heart and the role of the sul- fonylurea gliclazide. Methods Streptozotocin（STZ）-induced type 2 diabetic male Wistar rats with or without gliclazide （64 mg/kg body weight, orally） and age-matched non-diabetic control rats were used for all studies. The isolated hearts were perfused with Langendorff＇s system under the constant flow, pressure and tempera- ture conditions with Kreb＇s-Henseleit solution （K-H）. After 5 minutes of balance peffusion, these rats were randomly divided into six groups： non-diabetic control rats without IPC （CIR） ; non-diabetic control rats with IPC （CIP）; diabetic rats without 1PC （DIR）; diabetic rats with IPC （DIP）; gliclazide-treated diabetic rats without IPC （GIR）; and gliclazide-treated diabetic rats with IPC （GIP）. Groups CIR, DIR, and GIR were subjected to 30-rain global ischemia and 60-rain reperfusion for induction of ischemia/reperfusion injury. Groups CIP, DIP, and GIP were given three cycles of 5-min ischemia and 5-rain reperfusion as IPC, and then ischemia/reperfusion injury program was implemented. Extent of ischemia/reperfusion injury was measured in terms of the release of lactate dehydrogenase （LDH）, creatine kinase （CK）, and creatin kinase-MB （CK- MB） in coronary effluent. After perfusion, Kir6.2 and SUR2A mRNA expressions in the myocardial tissue were characterized by fluorescent quantitative real-time PCR method, and Kir6.2 and SUR2A protein expres- sions were assessed by immunohistochemistry. Result In non-diabetic control rats, the release of LDH, CK, and CK-MB in coronary effluent markedly decreased with IPC compared with No-IPC （P 〈 0.05）, but not in diabetic rats. However, in gliclazide-treated diabetic rats, IPC-induced decrease in the release of LDH, CK, and CK-MB was restored compared with No-IPC （P 〈 0.05）. The expressions of Kir6.2 both at mRNA and protein levels in CIP were significantly higher than those in CIR. There was no significant difference in theexpression of Kir6.2 and SUR2A both at mRNA and protein levels between DIP and DIR. However, the expression of Kir6.2 both at mRNA and protein levels was significantly higher in GIP than in GIR. No significant difference was detected in the mRNA expression level of SUR2A between the six groups. The expression of SUR2A at protein level was significantly higher in CIP than in CIR and in GIP than in GIR. Conclusions The cardioprotective effect of IPC is abolished in the isolated type 2 diabetic rats compared with non-diabetic control rats. However, to some extent, gliclazide can improve the myocardial protection of IPC against ischemia/reperfusion injury, thus suggesting that it is mediated mainly by KATP channels at mRNA or protein level, which provides a basis for further investigating the effects of KATP channels on IPC.

Effects of timely insulin treatment on protection of β cells in a rat model of type 2 diabetes mellitus

Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients with newly diagnosed type 2 diabetes. The purpose of this study was to investigate the effects of early insulin treatment on insulin mRNA expression and morphological alterations of β cells in a Sprague Dawley (SD) rat model of type 2 diabetes. Methods A rat model of type 2 diabetes mellitus (T2DM) was induced by a high fat diet (high energy, HE) and low doses of streptozotoxin (STZ, 40 mg/kg). A group of diabetic rats was then injected with protamine zinc insulin (PZI, 1-2 U·kg -1·d -1) for one week. Insulin mRNA expression, morphological features of pancreatic islets, and metabolic parameters were examined in rats using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and other techniques. Results In insulin-treated diabetic rats, insulin mRNA levels prominently increased by 81.3% (P<0.05), as compared with untreated diabetic rats. Moreover, timely insulin treatment noticeably improved the insulin content of β cells, with an increase of 10.2% (P<0.05), despite a slight reduction in fasting blood glucose (FBG), triglyceride (TG), and free fatty acid (FFA) levels, as compared to an untreated diabetic group. Conclusion Insulin treatment at the onset of T2DM effectively improves insulin synthesis, as confirmed by morphological changes to β cells in a rat model of type 2 diabetes.