scholarly journals Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yogendra Nayak ◽  
Venkatachalam Hillemane ◽  
Vijay Kumar Daroji ◽  
B. S. Jayashree ◽  
M. K. Unnikrishnan

Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D) was induced in Wistar rats by streptozotocin (60 mg/kg, i.p.) followed by nicotinamide (120 mg/kg i.p.). Rats having fasting blood glucose (FBG) >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR) was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

2019 ◽  
Vol 18 (3) ◽  
pp. 247-255
Author(s):  
Sierra-Puente D. ◽  
Abadi-Alfie S. ◽  
Arakanchi-Altaled K. ◽  
Bogard-Brondo M. ◽  
García-Lascurain M. ◽  
...  

Spices such as cinnamon (Cinnamomum Spp.) have been of interest due to their phytochemical composition that exert hypoglycemic effects with potential for management of type 2 diabetes mellitus (T2DM). We summarize data from 27 manuscripts that include, one book chapter, 3 review articles, 10 randomized controlled trials, 4 systematic reviews with meta-analysis, and 9 preclinical studies. The most frequently used cinnamon variety was Cinnamomum cassia rather than the Cinnamomum zeylanicum, whereas outcomes were defined as fasting blood glucose, glycated hemoglobin, and oral glucose tolerance test. A great variability in methodology such as different doses (from 120 mg to 6 g), duration of intervention, data retrieved and use of different concomitant medication, were found to be key aspects of most of trials and systematic reviews with meta-analysis available to date. Low quality studies have been made in most cases with a lot of heterogeneity clouding significance of results. More research needs to be done in order to yield accurate evidence for evidence-based recommendations. Its use is not currently a reliable nor advisable option for the treatment of T2DM.


2018 ◽  
Vol 315 (6) ◽  
pp. E1242-E1250 ◽  
Author(s):  
Donghua Hu ◽  
Ryan D. Russell ◽  
Devika Remash ◽  
Timothy Greenaway ◽  
Stephen Rattigan ◽  
...  

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.


Author(s):  
HODA A. ALI ◽  
SAHAR H. MOHAMED ◽  
HEND F. ALHARBI ◽  
REHAM M. ALGHESHAIRY

Objective: This study aims to explore the adjuvant effect of multi-strain probiotics with either saffron, cardamom, ginger, or cinnamon herbs to achieve synergistic management for controlling type 2 diabetes (T2D). Methods: Eighty-eight adult male, Wistar rats were used. Eight rats were kept as healthy control. Eighty rats were used to induce type 2 diabetic rats (T2DR) and were randomly assigned to ten groups. One group was an offer to 0.2 ml multi-strain probiotics orally. The rest of T2DR were gavage with 100 mg/kg aqueous extract of saffron, cardamom, ginger, or cinnamon without or with 0.2 ml multi-strain probiotics orally. Bodyweight gain (BWG), and feed efficiency ratio (FER) were recorded. Determination of oral glucose tolerance test (OGTT), serum insulin, C-peptide, HDL, LDL, HDL/total cholesterol ratio were performed. Serum antioxidant activity, Th1and Th2 cytokines and histopathology of the pancreas were done. Results: Comparable with T2DR, solely multi-strain probiotics or with herbs caused a significant reduction in BWG (P<0.05). Groups fed saffron, cardamom, and ginger and enriched with multi-strain probiotic showed significant improvement in OGTT, serum insulin, C-peptide and lipid abnormalities (P<0.05) compared to T2DR. Besides, they had antioxidant and anti-inflammatory effects. The group received ginger alone exerted anti-hyperglycemia and anti-inflammatory effects. However, cinnamon had a moderate anti-diabetic effect and solely probiotics did not show a significant benefit for all parameters except BWG. Conclusion: Cardamom, saffron, and ginger enriched with multi-strain probiotics achieve a synergistic relationship for managing T2D. This finding exhibits a possible new hypothesis to manage diabetes that needs further study.


2021 ◽  
Author(s):  
Hong Wang ◽  
Jie Cao ◽  
Jian-bin Su ◽  
Xueqin Wang ◽  
Dong-mei Zhang ◽  
...  

Background: Antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and serum AT3 activity was found to be decreased at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity indices and serum AT3 activity in patients with T2D. Methods: We conducted a cross-sectional study in patients with T2D who consented to participate in the study at the Endocrinology Department of Affiliated 2 Hospital of Nantong University from January 2015 to June 2018. All patients received serum AT3 activity test and 75-g oral glucose tolerance test (OGTT). Basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISIMatsuda), respectively, from the OGTT. And other relevant clinical data were also collected. Results: Total 1612 patients with T2D were enrolled in the study, with a mean age of 58.67±13.09 years and a median diabetes duration of 6 years (interquartile range, 1–10 years). Across ascending quartiles of serum AT3, HOMA-IR progressively decreased, while ISIMatsuda progressively increased (all p for trend <0.001). Moreover, serum AT3 was negatively correlated with HOMA-IR (r= –0.189, p<0.001) and positively correlated with ISIMatsuda (r=0.221, p<0.001). After adjusting for other metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate liner regression analysis, HOMA-IR (β= −0.185, t= −5.960, p<0.001) and ISIMatsuda (β= 0.197, t=6.632, p<0.001) remained independently associated with the serum AT3 activity in patients with T2D, respectively. Conclusions: Reduced basal and systemic insulin sensitivity are associated with decreased serum AT3 activity in patients with T2D.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Peng-ying Gu ◽  
Dong-mei Kang ◽  
Wei-dong Wang ◽  
Yan Chen ◽  
Zhi-hong Zhao ◽  
...  

We investigated the correlation between obestatin and metabolic parameters and carotid intima-media thickness (IMT) in plasma of patients with type 2 diabetes mellitus (T2DM). We collected 103 patients aged from 60 to 83 years (69.26 ± 5.83 years) form January, 2007 to May, 2009. All patients were divided into normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM according to the oral glucose tolerance test (OGTT). We found that higher levels of fasting insulin (Fins), fasting blood glucose, 2 h OGTT glucose, homeostasis model assessment of insulin resistance (HOMA-IR), low density lipoprotein cholesterol, glycated haemoglobin, and C-reactive protein (CRP), as well as lower obestatin level and higher intima-media thickness level (IMT), existed in T2DM group compared with NGT group and IGT group (P<0.01). Also, obestatin level was independently associated with HOMA-IR and CRP, while IMT level was independently associated with HOMA-IR, triglyceride, Fins, and obestatin (P<0.01), based on stepwise multiple regression analysis. Therefore, we deduced that the low level of plasma obestatin might be related to early arteriosclerosis in patients with T2DM via increasing IMT level, and elevated plasma obestatin levels might protect T2DM patients against carotid atherosclerosis to some extent.


Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1609
Author(s):  
Shinu Pottathil ◽  
Parminder Nain ◽  
Mohamed A. Morsy ◽  
Jaspreet Kaur ◽  
Bandar E. Al-Dhubiab ◽  
...  

The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL (100, 200, 400, and 600 mg/kg) were administered orally to diabetic rats for 45 days on a daily basis. The antidiabetic effect of MEPGL was examined by measuring blood glucose, plasma insulin, and glycated hemoglobin (HbA1c) levels, as well as with an oral glucose tolerance test. The antioxidant effect of MEPGL was determined by analyzing hepatic and renal antioxidant markers, namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation. The other biochemical markers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, and creatinine, as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. Type 2 diabetes significantly altered these parameters, while oral administration of the MEPGL significantly ameliorated them. Moreover, the pancreatic histopathological changes were attenuated with MEPGL treatment. In a nutshell, oral MEPGL administration in diabetic rats showed antidiabetic activity due to its antioxidant activity, most probably due to the gallic acid, ellagic acid, and apigenin found in MEPGL.


2021 ◽  
Author(s):  
Hong Wang ◽  
Jie Cao ◽  
Jian-bin Su ◽  
Xue-qin Wang ◽  
Dong-mei Zhang ◽  
...  

Abstract Background: Serum antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and AT3 activity was found to be decreased at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity and serum AT3 activity in patients with T2D. Methods: We recruited 1612 patients with T2D for this cross-sectional study from the Second Affiliated Hospital of Nantong University. All patients performed 75-g oral glucose tolerance test (OGTT), and basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISI Matsuda ), respectively. Serum AT3, one of the hemostatic parameters, and the relevant clinical data were collected, as well as other laboratory indicators. Results: It is showed that HOMA-IR decreased, while ISI Matsuda notably increased, across ascending quartiles of serum AT3. Moreover, serum AT3 were was negatively correlated with (r = –0.189, p < 0.001) and positively correlated with ISI Matsuda (r = 0.221, p < 0.001). After adjusted for metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate liner regression analysis, HOMA-IR (β = −0.179, t = −5.823, p < 0.001) and ISI Matsuda (β = 0.191, t = 6.395, p < 0.001) was remained independently associated with the serum AT3 activity patients with T2D, respectively. Conclusions: Reduced basal and systemic insulin sensitivity are associated with decreased AT3 activity in patients with T2D.


2017 ◽  
Vol 131 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Yong Luo ◽  
Ling Li ◽  
Xiaohui Xu ◽  
Tong Wu ◽  
Mengliu Yang ◽  
...  

Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic–hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time (RT)-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a glucagon-like peptide-1 (GLP-1) receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulating BMP-9 levels were significantly higher in healthy subjects than in newly diagnosed patients with T2DM. Circulating BMP-9 negatively correlated with HbA1c, fasting blood glucose (FBG), OGTT, the area under the curve for glucose (AUCglucose) and homoeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression analyses showed that BMP-9 levels were independently associated with non-esterified fatty acid (NEFA) and AUCglucose. Both hyperinsulinaemia and lipid infusion decreased circulating BMP-9 levels. BMP-9 mRNA and protein expressions were significantly decreased in muscle and adipose tissues of T2DM patients. In the placebo treated group, BMP-9 levels continued to decline over time, whereas in the PEX 168 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Henderikus E. Boersma ◽  
Robert P. van Waateringe ◽  
Melanie M. van der Klauw ◽  
Reindert Graaff ◽  
Andrew D. Paterson ◽  
...  

Abstract Background Skin autofluorescence (SAF) is a non-invasive marker of tissue accumulation of advanced glycation endproducts (AGE). Recently, we demonstrated in the general population that elevated SAF levels predict the development of type 2 diabetes (T2D), cardiovascular disease (CVD) and mortality. We evaluated whether elevated SAF may predict the development of CVD and mortality in individuals with T2D. Methods We included 2349 people with T2D, available baseline SAF measurements (measured with the AGE reader) and follow-up data from the Lifelines Cohort Study. Of them, 2071 had no clinical CVD at baseline. 60% were already diagnosed with diabetes (median duration 5, IQR 2–9 years), while 40% were detected during the baseline examination by elevated fasting blood glucose ≥7.0 mmol/l) and/or HbA1c ≥6.5% (48 mmol/mol). Results Mean (±SD) age was 57 ± 12 yrs., BMI 30.2 ± 5.4 kg/m2. 11% of participants with known T2D were treated with diet, the others used oral glucose-lowering medication, with or without insulin; 6% was using insulin alone. Participants with known T2D had higher SAF than those with newly-detected T2D (SAF Z-score 0.56 ± 0.99 vs 0.34 ± 0.89 AU, p < 0.001), which reflects a longer duration of hyperglycaemia in the former group. Participants with existing CVD and T2D had the highest SAF Z-score: 0.78 ± 1.25 AU. During a median follow-up of 3.7 yrs., 195 (7.6%) developed an atherosclerotic CVD event, while 137 (5.4%) died. SAF was strongly associated with the combined outcome of a new CVD event or mortality (OR 2.59, 95% CI 2.10–3.20, p < 0.001), as well as incidence of CVD (OR 2.05, 95% CI 1.61–2.61, p < 0.001) and death (OR 2.98, 2.25–3.94, p < 0.001) as a single outcome. In multivariable analysis for the combined endpoint, SAF retained its significance when sex, systolic blood pressure, HbA1c, total cholesterol, eGFR, as well as antihypertensive and statin medication were included. In a similar multivariable model, SAF was independently associated with mortality as a single outcome, but not with incident CVD. Conclusions Measuring SAF can assist in prediction of incident cardiovascular disease and mortality in individuals with T2D. SAF showed a stronger association with future CVD events and mortality than cholesterol or blood pressure levels.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2131
Author(s):  
Shujuan Zheng ◽  
Yanan Wang ◽  
Jingjing Fang ◽  
Ruixuan Geng ◽  
Mengjie Li ◽  
...  

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment–insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.


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