scholarly journals CCR2 antagonist CCX140-B provides renal and glycemic benefits in diabetic transgenic human CCR2 knockin mice

2013 ◽  
Vol 305 (9) ◽  
pp. F1288-F1297 ◽  
Author(s):  
Timothy Sullivan ◽  
Zhenhua Miao ◽  
Daniel J. Dairaghi ◽  
Antoni Krasinski ◽  
Yu Wang ◽  
...  
Keyword(s):  
Renal Function ◽  
Blood Glucose ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Fasting Blood Glucose ◽  
Model Assessment ◽  
Blood Monocytes ◽  
Glucose Levels ◽  
Homeostatic Model Assessment ◽  
Ccr2 Antagonist

Chemokine (C-C motif) receptor 2 (CCR2) is central for the migration of monocytes into inflamed tissues. The novel CCR2 antagonist CCX140-B, which is currently in two separate phase 2 clinical trials in diabetic nephropathy, has recently been shown to reduce hemoglobin A1c and fasting blood glucose levels in type 2 diabetics. In this report, we describe the effects of this compound on glycemic and renal function parameters in diabetic mice. Since CCX140-B has a low affinity for mouse CCR2, transgenic human CCR2 knockin mice were generated and rendered diabetic with either a high-fat diet (diet-induced obesity) or by deletion of the leptin receptor gene ( db/ db). CCX140-B treatment in both models resulted in decreased albuminuria, which was associated with decreased glomerular hypertrophy and increased podocyte density. Moreover, treatment of diet-induced obese mice with CCX140-B resulted in decreased levels of fasting blood glucose and insulin, normalization of homeostatic model assessment of insulin resistance values, and decreased numbers of adipose tissue inflammatory macrophages. Unlike other CCR2 antagonists, CCX140-B had no effect on plasma levels of the CCR2 ligand CCL2 or on the numbers of blood monocytes. These results support the ongoing evaluation of this molecule in diabetic subjects with impaired renal function.

scholarly journals Effect of Probiotics on the Glucose Levels of Pregnant Women: A Meta-Analysis of Randomized Controlled Trials

Medicina ◽  
2018 ◽  
Vol 54 (5) ◽  
pp. 77 ◽  
Author(s):  
Tzu-Rong Peng ◽  
Ta-Wei Wu ◽  
You-Chen Chao
Keyword(s):  
Blood Glucose ◽  
Randomized Controlled Trials ◽  
Pregnant Women ◽  
Cell Function ◽  
Fasting Blood Glucose ◽  
Controlled Trials ◽  
Model Assessment ◽  
Glucose Levels ◽  
Randomized Controlled ◽  
Blood Glucose Levels

Background: Gestational diabetes mellitus (GDM) is a condition, in which women develop high blood sugar levels during pregnancy without having diabetes. Evidence on the effects of probiotics on the blood glucose levels of women with GDM is inconsistent. Objective: The present study aimed to investigate the effects of probiotics on the blood glucose levels of pregnant women. Methods: Online databases, such as PubMed, Cochrane, and Excerpta Medica Database (EMBASE) were searched for randomized controlled trials (RCTs) published before July 2018. Trials had to meet the inclusion criteria of our study. Methodological quality and risk bias were independently assessed by two reviewers. Data were pooled using a random effects model and were expressed as the mean difference (MD) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as I2. Results: In total, 12 RCTs were included in this study. Studies have shown that the use of probiotics significantly reduced the fasting blood glucose (FBG) level (MD: −0.10 mmol/L; 95% CI: −0.19, −0.02), insulin concentration (MD: −2.24 μIU/mL; 95% CI: −3.69, −0.79), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score (MD: −0.47; 95% CI: −0.74, −0.21), and Homeostasis model of assessment-estimated β cell function (HOMA-B) score (MD: −20.23; 95% CI: −31.98, −8.49) of pregnant women. In a subgroup analysis, whether the blood glucose-lowering effect of probiotics influenced the diagnosis of pregnant women with GDM was assessed. The results showed that probiotics had significantly reduced the fasting blood glucose (FBG) level (MD: −0.10 mmol/L; 95% CI: −0.17, −0.04) and HOMA-IR score (MD: −0.37; 95% CI: −0.72, −0.02) of pregnant women who were not diagnosed with GDM. Conclusion: Probiotics reduce the blood glucose level of pregnant women, especially without GDM diagnosis. However, further research using RCTs must be conducted to validate the results of the present study.

scholarly journals Revealing the Hypoglycemic Effects and Mechanism of GABA-Rich Germinated Adzuki Beans on T2DM Mice by Untargeted Serum Metabolomics

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiujie Jiang ◽  
Qingpeng Xu ◽  
Aiwu Zhang ◽  
Yong Liu ◽  
Zhijiang Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Metabolic Pathways ◽  
Fasting Blood Glucose ◽  
Pathway Enrichment Analysis ◽  
Model Assessment ◽  
Public Attention ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases, and exploring strategies to prevent and treat diabetes has become extremely important. In recent decades the search for new therapeutic strategies for T2DM involving dietary interventions has attracted public attention. We established a diabetic mouse model by feeding mice a high-fat diet combined with injection of low-dose streptozotocin, intending to elucidate the effects and possible mechanisms of different dosages of γ-aminobutyric acid (GABA)-rich germinated adzuki beans on the treatment of diabetes in mice. The mice were treated for 6 weeks either with increasing doses of GABA-enriched germinated adzuki beans, with non-germinated adzuki beans, with GABA, or with the positive control drug metformin. Then, the blood glucose levels and blood lipid biochemical indicators of all the mice were measured. At the same time, serum differential metabolite interactions were explored by UPLC-Q/TOF-MS-based serum metabolomic analysis. The results showed that body weight and fasting blood glucose levels were significantly reduced (P < 0.05). We also report improved levels of total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, urea, and serum creatinine. We observed a significant improvement in the homeostasis model assessment of the beta cell function and insulin resistance (HOMA-β and HOMA-IR) scores (P < 0.05) in the group of mice treated with the highest dose of GABA-enriched germinated adzuki beans. In addition, the metabolic profiles of the serum were analyzed, and 31 differential metabolites including amino acids and lipids were obtained. According to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, this was found to be correlated with nine significantly enriched metabolic pathways involving the up-regulation of levels of L-serine, SM (d18:1/22:1(13Z)), L-histidine, creatine, and 3-indoleacetic acid. Our data suggest that the hypoglycemic effect of GABA-enriched germinated adzuki beans on diabetic mice may be related to improving tryptophan metabolism, glycerol phospholipid metabolism, sphingosline metabolism, and the glycine, serine, and threonine metabolic pathways. This study provides a reference for the application of GABA-enriched germinated foods in type 2 diabetes and could provide a cue for searching biomarkers to be adopted for T2DM diagnosis.

scholarly journals Effects of green coffee extract on fasting blood glucose, insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR): a systematic review and meta-analysis of interventional studies

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Omid Nikpayam ◽  
Marziyeh Najafi ◽  
Samad Ghaffari ◽  
Mohammad Asghari Jafarabadi ◽  
Golbon Sohrab ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Meta Analysis ◽  
Fasting Blood Glucose ◽  
Experimental Studies ◽  
Current Evidence ◽  
Model Assessment ◽  
Green Coffee ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model

Abstract Many studies have investigated the relationship between coffee and diabetes. Evaluation of the current evidence on the effect of coffee intake on diabetes is critical. Therefore, we aimed to investigate the potential association between green coffee extract (GCE) and fasting blood glucose (FBG), insulin and homeostatic model assessment of insulin resistance (HOMA-IR) by pooling together the results from clinical trials. PubMed, Scopus and Google Scholar were searched for experimental studies which have been published up to December 2018. Randomized controlled trials (RCTs) that investigated the effect of GCE supplementation on FBG, insulin and HOMA-IR in adults were included for final analysis. A total of six articles were included in the meta-analysis. Results revealed that GCE supplementation reduced FBG level (SMD: −0.32, 95% CI − 0.59 to − 0.05, P = 0.02) but had no effect on insulin levels (SMD: −0.22, 95% CI −0.53 to 0.09, P = 0.159). Although analysis showed that GCE supplementation cannot change the HOMA-IR status (SMD: −0.30, 95% CI −0.73 to 0.13, P = 0.172), after stratified studies by GCE dosage (< 400 mg/day versus > 400 mg/day) there was a significant decrease in HOMA-IR status in a dose greater than 400 mg. These findings suggest that GCE intake might be associated with FBG improvement.

scholarly journals The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pattawika Lertpatipanpong ◽  
Jaehak Lee ◽  
Ilju Kim ◽  
Thomas Eling ◽  
Seung Yeon Oh ◽  
...  
Keyword(s):  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Immunohistochemical Analysis ◽  
Diabetic Mouse ◽  
Mrna Levels ◽  
Model Assessment ◽  
Glucose Levels ◽  
Lower Body Weight ◽  
Homeostatic Model Assessment ◽  
Beta Cell Area

AbstractNonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasting blood glucose levels, and serum insulin levels than wild-type (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were lower than those of WT mice. Hematoxylin and eosin staining revealed a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas of NAG-1 Tg mice than in those of WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. Adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the expression of IRS1/PI3K/AKT signaling pathway components, especially Foxo1, which regulates gluconeogenesis in the muscle and white adipose tissue, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted the expression of As160 in both muscles and adipocytes, and the mRNA levels of the NLRP3 pathway members were downregulated in NAG-1 Tg mice. Our findings suggest that NAG-1 expression alleviates diabetes in mice.

scholarly journals Impact of Dairy Intake on Plasma F2-IsoProstane Profiles in Overweight Subjects with Hyperinsulinemia: A Randomized Crossover Trial

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2088
Author(s):  
Leila Khorraminezhad ◽  
Jean-François Bilodeau ◽  
Karine Greffard ◽  
Jessica Larose ◽  
Iwona Rudkowska
Keyword(s):  
Blood Glucose ◽  
Plasma Levels ◽  
Dairy Product ◽  
Fasting Blood Glucose ◽  
Model Assessment ◽  
Dairy Intake ◽  
Homeostatic Model Assessment ◽  
Study Participants ◽  
Overweight Subjects

F2-IsoProstanes (F2-IsoPs) are major biomarkers of oxidative stress and are associated with type 2 diabetes (T2D). Further, plasma levels of F2-IsoPs may be modified by dairy products. The aim is to investigate the effect of high dairy product (HD) consumption compared to an adequate dairy product (AD) consumption on the level of F2-IsoPs among hyperinsulinemic subjects. In this crossover study, participants were randomized in two groups: HD (≥4 servings/day), or AD (≤2 servings/day) for six weeks. Fasting blood glucose and insulin were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Six isomers of F2-IsoPs were quantified by HPLC-MS/MS. Twenty-seven subjects with hyperinsulinemia (mean age; 55 ± 13 years, BMI; 31.4 ± 3.3 kg/m2) were included. Fasting glucose, insulin and HOMA-IR were unchanged after HD or AD intervention. After HD intake, the total level of F2-IsoPs (p = 0.03), 5-F2t-IsoP (p = 0.002), and 8-F2t-IsoP (p = 0.004) decreased compared to AD. The 15-F2t-IsoP tended to be positively correlated with fasting blood glucose (r = 0.39, p = 0.08). Generally, F2-IsoPs levels were higher among men compared to women regardless of the dairy intake. Overall, intake of HD decreased plasma levels of F2-IsoPs compared to AD without modifying glycemic parameters.

scholarly journals Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people

2016 ◽  
Vol 115 (8) ◽  
pp. 1379-1386 ◽  
Author(s):  
Kylie A. Abbott ◽  
Martin Veysey ◽  
Mark Lucock ◽  
Suzanne Niblett ◽  
Katrina King ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Model Assessment ◽  
Dietary Interventions ◽  
Overweight Women ◽  
Overweight People ◽  
Homeostatic Model Assessment

AbstractThe association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46·3 % female; 76·7 (sd 5·9) years) and 466 non-diabetic (57·9 % female; 77·8 (sd 7·1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1·0 (reference), 0·82 (95 % CI 0·31, 2·18), 0·56 (95 % CI 0·21, 1·52) and 0·22 (95 % CI 0·06, 0·82) (Ptrend=0·015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences.

Detection of Glucose in Human Serum Based on Silicon Dot Probe

2020 ◽  
Vol 16 (6) ◽  
pp. 744-752
Author(s):  
Kuan Luo ◽  
Xinyu Jiang
Keyword(s):  
Quantum Dots ◽  
Blood Glucose ◽  
Human Serum ◽  
Organic Dyes ◽  
Limit Of Detection ◽  
Fasting Blood Glucose ◽  
Glucose Biosensor ◽  
Metal Nanoclusters ◽  
Glucose Levels ◽  
Highly Sensitive

Background: Diabetes Mellitus (DM) is a major public metabolic disease that influences 366 million people in the world in 2011, and this number is predicted to rise to 552 million in 2030. DM is clinically diagnosed by a fasting blood glucose that is equal or greater than 7 mM. Therefore, the development of effective glucose biosensor has attracted extensive attention worldwide. Fluorescence- based strategies have sparked tremendous interest due to their rapid response, facile operation, and excellent sensitivity. Many fluorescent compounds have been employed for precise analysis of glucose, including quantum dots, noble metal nanoclusters, up-converting nanoparticles, organic dyes, and composite fluorescent microspheres. Silicon dot as promising quantum dots materials have received extensive attention, owing to their distinct advantages such as biocompatibility, low toxicity and high photostability. Methods: MnO2 nanosheets on the Si nanoparticles (NPs) surface serve as a quencher. Si NPs fluorescence can make a recovery by the addition of H2O2, which can reduce MnO2 to Mn2+, and the glucose can thus be monitored based on the enzymatic conversion of glucose by glucose oxidase to generate H2O2. Therefore, the glucose concentration can be derived by recording the fluorescence recovery spectra of the Si NPs. Results: This probe enabled selective detection of glucose with a linear range of 1-100 μg/mL and a limit of detection of 0.98 μg/mL. Compared with the commercial glucometer, this method showed favorable results and convincing reliability. Conclusion: We have developed a novel method based on MnO2 -nanosheet-modified Si NPs for rapid monitoring of blood glucose levels. By combining the highly sensitive H2O2/MnO2 reaction with the excellent photostability of Si NPs, a highly sensitive, selective, and cost-efficient sensing approach for glucose detection has been designed and applied to monitor glucose levels in human serum with satisfactory results.

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