An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.

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Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats

Journal of Diabetes Research ◽

10.1155/2014/196312 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Xiaofei Huang ◽

Pan Weng ◽

Huixin Zhang ◽

Yingli Lu

Keyword(s):

Type 2 Diabetes ◽

Sleeve Gastrectomy ◽

Blood Glucose ◽

Glucose Metabolism ◽

Fasting Blood Glucose ◽

Blood Glucose Control ◽

Intestinal Flora ◽

Diabetic Rats ◽

Sham Operation

Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats.Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals’ weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis.Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy.Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism.

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Anti-hyperglycemic activity of Aegle marmelos (L.) corr. is partly mediated by increased insulin secretion, α-amylase inhibition, and retardation of glucose absorption

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0160 ◽

2017 ◽

Vol 30 (1) ◽

Cited By ~ 9

Author(s):

Prawej Ansari ◽

Nadia Afroz ◽

Shahnaz Jalil ◽

Sohel Bin Azad ◽

Md. Gazi Mustakim ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Tolerance ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Plasma Insulin Concentration ◽

Oral Sucrose ◽

Type 2 Diabetic

AbstractBackground:(commonly known as Bael, golden apple) was formerly described to have anti-hyperglycemic activity. The present study aimed to explore the possible effects, in depth, ofMethods:This research begins with fasting blood glucose and oral glucose tolerance test (OGTT) to evaluate the primary anti-hyperglycemic effect in chemically induced type 2 diabetic rats. Furthermore, the plasma insulin concentration and serum glucose level were studied, which include measuring the sucrose content in six different segments of the gastrointestinal (GI) tract of the rats following oral sucrose feeding. An in situ, perfused, intestinal model in rats and glucose-fiber binding assay were conducted to find the effects ofResults:Treatment of extracts suppressed blood glucose elevation after oral sucrose (2.5 g/kg) administration and significantly (p<0.05) improved oral glucose tolerance in type 2 diabetic rats.Conclusions:The findings demonstrate that anti-hyperglycemic activity of

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Pre-impaired Fasting Glucose State Is A Risk Factr for Endothelial Dysfunction Flow-mediated Dilation Japan (FMD-J) Study

10.21203/rs.3.rs-30721/v1 ◽

2020 ◽

Author(s):

Takayuki Yamaji ◽

Takahiro Harada ◽

Yu Hashimoto ◽

Yuji Takaeko ◽

Masato Kajikawa ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Endothelial Dysfunction ◽

Impaired Fasting Glucose ◽

Fasting Glucose ◽

Fasting Blood Glucose ◽

Large Sample Size ◽

Clinical Trial Registry ◽

Significant Difference

Abstract Background There is little information on the relationships of fasting blood glucose (FBG) including high normal blood glucose and impaired fasting glucose (IFG) with endothelial function. The purpose of this study was to evaluate the relationship between FBG level and flow-mediated vasodilation (FMD) in detail using a large sample size. Methods This study was a cross-sectional study. We measured FMD in 7265 subjects at 31 general hospitals. The subjects were divided into four groups based on FBG levels: <5.55 mmol/L, 5.55–6.05 mmol/L, 6.11–6.94 mmol/L, and ≥ 6.99 mmol/L or known type 2 diabetes. The subjects were also divided into six groups based on FBG levels: <5.00 mmol/L, 5.00-5.22 mmol/L, 5.27–5.50 mmol/L, 5.55–6.05 mmol/L, 6.11–6.94 mmol/L, and ≥ 6.99 mmol/L or known type 2 diabetes. Results FMD decreased in relation to increase in FBG level. There was a significant difference in FMD between the FBG of < 5.55 mmol/L group and the other three groups (6.7 ± 3.1% vs. 5.9 ± 2.8%, 5.7 ± 3.1%, and 5.1 ± 2.6%; p < 0.001, respectively). After adjustment for confounding factors, the odds of having the lowest quartile of FMD was significantly higher in the FBG of 5.27–5.50 mmol/L, 5.55–6.05 mmol/L, 6.11–6.94 mmol/L, and ≥ 6.99 mmol/L or known type 2 diabetes groups than in the FBG of < 5.00 mmol/L, group. Conclusions These findings suggest that FBG of 5.55–6.05 mmol/L and FBG of 6.11–6.94 mmol/L are similarly associated with endothelial dysfunction and that a pre-IFG state (FBG of 5.27–5.50 mmol/L) is also a risk for endothelial dysfunction compared with FBG of < 5.00 mmol/L. Clinical Trial Registry Information: http://www.umin.ac.jp (UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409)

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Tangduqing Granules Attenuate Insulin Resistance and Abnormal Lipid Metabolism through the Coordinated Regulation of PPARγ and DGAT2 in Type 2 Diabetic Rats

Journal of Diabetes Research ◽

10.1155/2019/7403978 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Qinghua Zhang ◽

Yingying Huang ◽

Xiaojin Li ◽

Hongyi Liu ◽

Baichuan He ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Lipid Metabolism ◽

Insulin Sensitivity ◽

Fasting Blood Glucose ◽

Diabetic Rat ◽

Lipid Metabolism Disorder ◽

Metabolism Disorder ◽

Type 2 Diabetic

Insulin resistance (IR) is a vital hallmark of type 2 diabetes mellitus, which is characterized by an impaired ability of insulin to promote glucose uptake and utilization. Lipid deposition is closely associated with impaired insulin sensitivity. PPARγ plays an important role in glucose homeostasis, adipocyte differentiation, and insulin sensitivity. Likewise, DGAT2 also exerts a crucial role in integrating carbohydrate and lipid metabolism in the liver. The present study is aimed at evaluating a Chinese medicinal formula, Tangduqing granules (TDQ), with multifaceted actions against lipid and glucose metabolism disorder and IR of type 2 diabetes. An animal model of type 2 diabetes was developed by high-fat diet feeding plus low-dose streptozotocin injection. After oral administration of TDQ for 5 weeks, the effects on glucose and lipid metabolism and the underlying mechanism were evaluated by biochemical, histological, RT-PCR, and western blotting methods. The results showed that TDQ decreased fasting blood glucose, ameliorated glucose tolerance, and improved IR. Besides, TDQ regulated hyperlipidemia symptoms, decreased serum lipid levels and liver TG, and reduced hepatic steatosis in a type 2 diabetic rat model. Furthermore, TDQ reversed diabetes-induced decrease in the mRNA and protein expression of PPARγ and elevation in the mRNA and protein levels of DGAT2 in the liver. In addition, we showed that interference of TDQ ameliorated palmitate-induced glucose and lipid metabolic abnormalities in HepG2 cells. TDQ are, therefore, a potential Chinese medicinal formula that relieves IR and lipid metabolism disorder might be through promotion of PPARγ and decrease of DGAT2 expression.

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Pyrrolidine dithiocarbamate enhances hepatic glycogen synthesis and reduces FoxO1-mediated gene transcription in type 2 diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00453.2011 ◽

2012 ◽

Vol 302 (4) ◽

pp. E409-E416 ◽

Cited By ~ 11

Author(s):

Tienian Zhu ◽

Ruijing Zhao ◽

Lizhong Zhang ◽

Michel Bernier ◽

Jiankun Liu

Keyword(s):

Blood Glucose ◽

Glycogen Synthesis ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Hepatic Glycogen ◽

Pyrrolidine Dithiocarbamate ◽

Glycogen Deposition ◽

Gsk 3Β ◽

Type 2 Diabetic

The aim of the present study was to examine the effects of pyrrolidine dithiocarbamate (PDTC) on hepatic glycogen synthesis and FoxO1 transcriptional activity in type 2 diabetic rats and the mechanism underlying these effects. Fasting blood glucose and glycogen deposition, together with expressions of two key genes related to gluconeogenesis, were studied in the liver of rats fed a normal diet (NC), high-fat diet (HFD)-induced insulin-resistant rats made type 2 diabetic by a single intraperitoneal injection of streptozotocin (DM), and a DM with intervention of PDTC (DM + PDTC) for 1 wk. The phosphorylation of Akt, GSK-3β, and FoxO1 was assessed in liver extracts of fasted rats by Western blot, whereas indirect immunofluorescence staining was performed to determine the cellular distribution of FoxO1. The DM rats exhibited obvious increases in fasting blood glucose as well as decreased hepatic glycogen content compared with the NC group. Activation of the Akt/GSK-3β pathway and inactivating phosphorylation of FoxO1 were reduced greatly in DM rat livers ( P < 0.01). By contrast, PDTC treatment protected DM rats against high fasting blood glucose and hepatic glycogen deposition loss. PDTC also elicited an increase in Akt/GSK-3β signaling and subsequent inactivation and nuclear export of FoxO1 in DM rat livers, which translated into a significant reduction in the expression of two FoxO1 target genes, phospho enolpyruvate carboxykinase and glucose-6-phosphatase. This study suggests that PDTC enhances hepatic glycogen synthesis, whereas it reduces FoxO1 transcriptional activity in DM rats.

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Increased H2S synthesizing activity in plasma correlated to fasting blood glucose levels: A study in type 2 diabetes patients

Asian Journal of Medical Sciences ◽

10.3126/ajms.v7i6.15193 ◽

2016 ◽

Vol 7 (6) ◽

pp. 6-10

Author(s):

Pinaki Saha ◽

Sayantan Dasgupta ◽

Sukla Nath ◽

Pradipta Ghosh ◽

Santanu Sen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Fasting Blood Glucose ◽

Small Sample ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Major Health Problem ◽

Type 2 Diabetic ◽

Diabetes Patients

Background: Diabetes mellitus is a major health problem not only in India but worldwide. Our country presently is undergoing an epidemic stage of this non-communicable disease.Though several etiological background of type 2 diabetes has been well explained, yet a number of recent literatures suggested a potential role H2S producing enzymes in the etiology and management of this metabolic disorder.Aims and Objectives: Our aim was to elucidate the relationship of H2S synthesizing activity in plasma and fasting blood glucose in type 2 diabetic patients. Materials and Methods: Sixty-two newly diagnosed type 2 diabetes patients and equal number of non-diabetic controls were included in the study. Enzymatic activity of synthesizing H2S in plasma was estimated following methods described earlier with further modification and standardization in our laboratory. All other parameters were estimated by using standardized kits.Results: FBG, PPBG, HbA1C, Fasting Insulin, H2S synthesizing activity in plasma in patients are significantly higher (p< 0.05) than the corresponding values in healthy controls H2S synthesizing activity in plasma is positively correlated with fasting plasma glucose and the correlations is significant(p=0.05).Conclusion: Our study though a pilot study with a small sample size, has elucidated that the values of H2S synthesizing activity in plasma are significantly elevated in type 2 diabetic patients and this may help researchers to develop H2S modifying agents and enzyme inhibitors which may open up new horizon in the treatment modalities of type 2 diabetes mellitus.Asian Journal of Medical Sciences Vol.7(6) 2016 6-10

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Effect of Exercise Training on Gene Expression of Adiponectin and its Receptors in Testicles and Sex Hormones in Diabetic Rats

Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale ◽

10.4081/jbr.2021.9287 ◽

2021 ◽

Author(s):

Zahra Nadi ◽

Mohammad Bayat ◽

Hadi Karami ◽

Mohamad Parastesh ◽

ParvinDokht Bayat

Keyword(s):

Gene Expression ◽

Blood Glucose ◽

Sex Hormones ◽

Fasting Blood Glucose ◽

Serum Testosterone ◽

Diabetic Rats ◽

Male Sex ◽

Group Resistance ◽

Type 2 Diabetic

Adiponectin and its receptors are expressed in the male reproductive system, which play a role in regulating male sex hormones and fertility. Diabetes was induced by Streptozotocin-Nicotinamide (STZ-NA i.p) in rats and after performing the trainings, adiponectin gene expression and its receptors in the testis were evaluated using real time PCR, and blood serum was then used in order to assess FSH, LH and testosterone. The STZ-NA significantly increased the fasting blood glucose, gene expression of adiponectin AdipoR1 in the testicles of diabetic rats. A significant reduction in serum testosterone and LH levels were observed in the diabetic group. Resistance and endurance training decreased blood glucose, adiponectin and AdipoR1 gene, and also increased the serum testosterone and LH levels in diabetic rats. Overall, our data suggest the role played by training in improve expression of adiponectin and AdipoR1 gene by increasing the serum testosterone and LH levels in type 2 diabetic rats.

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Effect of Exercise Training on Gene Expression of Adiponectin and its Receptors in Testicles and Sex Hormones in Diabetic Rats

Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale ◽

10.4081/jbr.0.9287 ◽

2021 ◽

Author(s):

Zahra Nadi ◽

Mohammad Bayat ◽

Hadi Karami ◽

Mohamad Parastesh ◽

ParvinDokht Bayat

Keyword(s):

Gene Expression ◽

Blood Glucose ◽

Sex Hormones ◽

Fasting Blood Glucose ◽

Serum Testosterone ◽

Diabetic Rats ◽

Male Sex ◽

Group Resistance ◽

Type 2 Diabetic

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Effect of heat-killed Streptococcus thermophilus on type 2 diabetes rats

PeerJ ◽

10.7717/peerj.7117 ◽

2019 ◽

Vol 7 ◽

pp. e7117 ◽

Cited By ~ 1

Author(s):

Xiangyang Gao ◽

Fei Wang ◽

Peng Zhao ◽

Rong Zhang ◽

Qiang Zeng

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiota ◽

Fasting Blood Glucose ◽

Streptococcus Thermophilus ◽

Diabetic Rats ◽

Inflammatory Factors ◽

Diabetic Rat ◽

Oral Glucose ◽

Zdf Rats

Background and Aims The link between gut microbiota and type 2 diabetes (T2D) has been addressed by numerous studies. Streptococcus thermophilus from fermented milk products, has been used as a probiotic in previous research. However, whether heat-killed S. thermophilus can improve the glycemic parameters of diabetic rats remains unanswered. In this study, we evaluated the effect of heat-killed S. thermophilus on T2D model rats and the potential mechanisms of the effect. Methods Zucker diabetic fatty (ZDF) rats were used to generate a diabetic rat model induced by feeding a high-fat diet. Heat-killed S. thermophilus were orally administered to normal and diabetic rats for 12 weeks. Intestinal microbiota analysis, histology analysis, oral glucose tolerance test and measurement of inflammatory factors were performed. Results We found that heat-killed S. thermophilus treatment reduced fasting blood glucose levels and alleviated glucose intolerance and total cholesterol in diabetic ZDF rats. Additionally, heat-killed S. thermophilus increased the interleukin 10 while reducing the levels of lipopolysaccharide, interleukin 6, and tumor necrosis factor-α in diabetic ZDF rats. The heat-killed S. thermophilus treatment can normalize the structure of the intestinal and colon mucosal layer of diabetic rats. The characteristics of the gut microbiota in heat-killed S. thermophilus-treated and control rats were similar. At the genus level, the abundances of beneficial bacteria, including Ruminococcaceae, Veillonella, Coprococcus, and Bamesiella, were all significantly elevated by heat-killed S. thermophilus treatment in ZDF diabetic rats. Conclusion Our study supports the hypothesis that treatment with heat-killed S. thermophilus could effectively improve glycemic parameters in T2D model rats. In addition, the potential mechanisms underlying the protection maybe include changing the composition of gut microbiota, reinforcing the intestinal epithelial barrier and the immunity of the intestinal mucosa, decreasing the level of inflammation, and then reducing the insulin resistance.

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Hypoglycaemic and Antioxidant Properties of Acrocomia aculeata (Jacq.) Lodd Ex Mart. Extract Are Associated with Better Vascular Function of Type 2 Diabetic Rats

Nutrients ◽

10.3390/nu13082856 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2856

Author(s):

Tamaeh Monteiro-Alfredo ◽

Sara Oliveira ◽

Andreia Amaro ◽

Daniela Rosendo-Silva ◽

Katia Antunes ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Vascular Function ◽

Therapeutic Potential ◽

Antioxidant Properties ◽

Diabetic Rats ◽

Antioxidant Defences ◽

Acrocomia Aculeata ◽

Type 2 Diabetic

Oxidative stress is involved in the metabolic dysregulation of type 2 diabetes (DM2). Acrocomia aculeata (Aa) fruit pulp has been described for the treatment of several diseases, and recently we have proved that its leaves have phenolic compounds with a marked antioxidant effect. We aimed to assess whether they can improve metabolic, redox and vascular functions in DM2. Control Wistar (W-Ctrl) and non-obese type 2 diabetic Goto–Kakizaki (GK-Ctrl) rats were treated for 30 days with 200 mg.kg−1 aqueous extract of Aa (EA-Aa) (Wistar, W-EA-Aa/GK, GK-EA-Aa). EA-Aa was able to reduce fasting glycaemia and triglycerides of GK-EA-Aa by improving proteins related to glucose and lipid metabolism, such as GLUT-4, PPARγ, AMPK, and IR, when compared to GK-Ctrl. It also improved viability of 3T3-L1 pre-adipocytes exposed by H2O2. EA-Aa also increased the levels of catalase in the aorta and kidney, reduced oxidative stress and increased relaxation of the aorta in GK-treated rats in relation to GK-Ctrl, in addition to the protective effect against oxidative stress in HMVec-D cells. We proved the direct antioxidant potential of the chemical compounds of EA-Aa, the increase in antioxidant defences in a tissue-specific manner and hypoglycaemic properties, improving vascular function in type 2 diabetes. EA-Aa and its constituents may have a therapeutic potential for the treatment of DM2 complications.

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