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 NAG-1/GDF15 Exerts Anti-diabetic Effects through the Insulin Signaling Pathway

2021 ◽  
Author(s):  
Pattawika Lertpatipanpong ◽  
Jaehak Lee ◽  
Thomas Eling ◽  
Seung Yon Oh ◽  
Je Kyung Seong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Fasting Blood Glucose ◽  
Immunohistochemical Analysis ◽  
Diabetic Mouse ◽  
Mrna Levels ◽  
Model Assessment ◽  
Homeostatic Model Assessment ◽  
Lipid Droplet Size ◽  
Hematoxylin And Eosin ◽  
Beta Cell Area

Abstract Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) has a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower bodyweight and fasting blood glucose and insulin levels than wildtype (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were three times lower than those of WT mice. Hematoxylin and eosin staining demonstrated that NAG-1 Tg mice exhibited a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas, compared to WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. The adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the IRS1/PI3K/AKT signaling pathway, especially Foxo1, which regulates gluconeogenesis in the muscle and WAT, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted As160 (AKT substrate of 160 kDa) expression 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 Bidens pilosaFormulation Improves Blood Homeostasis andβ-Cell Function in Men: A Pilot Study

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Bun-Yueh Lai ◽  
Tzung-Yan Chen ◽  
Shou-Hsien Huang ◽  
Tien-Fen Kuo ◽  
Ting-Hsiang Chang ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Cell Function ◽  
Serum Insulin ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Antidiabetic Activity ◽  
Model Assessment ◽  
Fasting Serum ◽  
Homeostatic Model Assessment ◽  
Animal Models Of Diabetes

B. pilosahas long been purported to have antidiabetes activity, but despite the advancement in phytochemistry and animal models of diabetes, no human clinical trials have been conducted to date. Here, we evaluated the effect of aB. pilosaformulation on fasting blood glucose (FBG), fasting serum insulin, and glycosylated hemoglobin A1c(HbA1c)in diabetic subjects. TheB. pilosaformulation reduced the level of FBG andHbA1cin diabetics but increased fasting serum insulin in healthy subjects. Moreover, combination ofB. pilosaformulation with antidiabetic drugs had better glycemic control in diabetics. The homeostatic model assessment (HOMA) data suggested that the antidiabetic activity of this formulation was via improvement ofβ-cell function. We also tested the safety of theB. pilosaformulation in healthy subjects and observed no obvious side effects. We conclude thatB. pilosahas potential as an antidiabetes treatment.

scholarly journals A Role for Oncostatin M in the Impairment of Glucose Homeostasis in Obesity

2019 ◽  
Vol 105 (3) ◽  
pp. e337-e348 ◽  
Author(s):  
Irene Piquer-Garcia ◽  
Laura Campderros ◽  
Siri D Taxerås ◽  
Aleix Gavaldà-Navarro ◽  
Rosario Pardo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Serum Insulin ◽  
Oncostatin M ◽  
Mrna Levels ◽  
Model Assessment ◽  
Human Adipocytes ◽  
Glucose Levels ◽  
Inflammatory State

Abstract Context Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood. Objective The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. Design 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels <100 mg/dL and (2) glucose levels >100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. Results OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. Conclusions OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.

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 Sam68 promotes hepatic gluconeogenesis via CRTC2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aijun Qiao ◽  
Junlan Zhou ◽  
Shiyue Xu ◽  
Wenxia Ma ◽  
Chan Boriboun ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Therapeutic Target ◽  
Rna Binding ◽  
Adaptor Protein ◽  
Diabetic Mouse ◽  
Mrna Levels ◽  
Hepatic Gluconeogenesis ◽  
Kinase Substrate ◽  
Glucose Levels ◽  
Patients With Diabetes

AbstractHepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68ΔC) or N-terminal (Sam68ΔN) domains fails to bind CRTC2 or to stabilize CRTC2 protein, respectively, and transgenic Sam68ΔN mice recapitulate the blood-glucose and gluconeogenesis profile of Sam68-deficient mice. Hepatic Sam68 expression is also upregulated in patients with diabetes and in two diabetic mouse models, while hepatocyte-specific Sam68 deficiencies alleviate diabetic hyperglycemia and improves insulin sensitivity in mice. Thus, our results identify a role for Sam68 in hepatic gluconeogenesis, and Sam68 may represent a therapeutic target for diabetes.

scholarly journals Serum Fibroblast Growth Factor 21 Levels Are Correlated with the Severity of Diabetic Retinopathy

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Yuan Lin ◽  
Ye-cheng Xiao ◽  
Hong Zhu ◽  
Qing-yan Xu ◽  
Lei Qi ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Serum Insulin ◽  
Conditional Logistic Regression ◽  
Fasting Blood Glucose ◽  
Fibroblast Growth Factor 21 ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Fibroblast Growth

The aim of the study was to assess serum fibroblast growth factor 21 (FGF21) concentrations in Chinese type 2 diabetic patients with and without retinopathy and to assess the association between FGF21 and the severity of retinopathy. 117 diabetic patients were compared with 68 healthy controls. Fasting blood glucose, serum total cholesterol, serum triglycerides, serum insulin, and serum FGF21 levels were estimated. FGF21 concentrations in the patients were significantly higher than those in control. In the patient group there was a significant positive correlation between FGF21, insulin level, and homeostasis model assessment index. Serum FGF21 concentrations in patients with proliferative diabetic retinopathy or nonproliferative diabetic retinopathy were significantly higher than those in patients without diabetic retinopathy. When the presence of diabetes was defined as the final variable in the conditional logistic regression model with the FGF21 concentration as the continuous variable, FGF21 was significantly involved in the model. This study shows that the increase in serum concentration of FGF21 was associated with the severity of diabetic retinopathy and suggests that FGF21 may play a role in the pathogenesis of diabetic retinopathy and its degree.

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 Effect of reduced dietary zinc intake on carbohydrate and Zn metabolism in the genetically diabetic mouse (C57BL/KsJ db+/db+)

1988 ◽  
Vol 60 (3) ◽  
pp. 499-507 ◽  
Author(s):  
Susan Southon ◽  
Z. Kechrid ◽  
A. J. A. Wright ◽  
Susan J. Fairweather-Tait
Keyword(s):  
Blood Glucose ◽  
Control Diet ◽  
Fasting Blood Glucose ◽  
Liver Glycogen ◽  
Diabetic Mouse ◽  
Whole Body ◽  
Diabetic Mice ◽  
Control Groups ◽  
Glucose Levels ◽  
Blood Glucose Levels

1. Male, 4–5-week-old, genetically diabetic mice (C57BL/KsJ db/db) and non-diabetic heterozygote litter-mates (C57BL/KsJ db/+)were fed on a diet containing 1 mg zinc/kg (low-Zn groups) or 54 mg Zn/kg (control groups) for 27 d. Food intakes and body-weight gain were recorded regularly. On day 28, after an overnight fast, animals were killed and blood glucose and insulin concentrations, liver glycogen, and femur and pancreatic Zn concentrations were determined.2. The consumption of the low-Zn diet had only a minimal effect on the Zn status of the mice as indicated by growth rate, food intake and femur and pancreatic Zn concentrations. In fact, diabetic mice fed on the low-Zn diet had a higher total food intake than those fed on the control diet. The low-Zn diabetic mice had higher fasting blood glucose and liver glycogen levels than their control counterparts. Fasting blood insulin concentration was unaffected by dietary regimen.3. A second experiment was performed in which the rate of loss of 65Zn, injected subcutaneously, was measured by whole-body counting in the two mouse genotypes over a 28 d period, from 4 to 5 weeks of age. The influence of feeding low-Zn or control diets was also examined. At the end of the study femur and pancreatic Zn and non-fasting blood glucose levels were determined.4. All mice fed on the low-Zn diet showed a marked reduction in whole-body 65Zn loss compared with those animals fed on the control diet. In the low-Zn groups, the loss of 65Zn from the diabetic mice was significantly greater than that from heterozygote mice. This difference was not observed in the control groups. Blood glucose levels were elevated in the low-Zn groups. Possible reasons for these observations are discussed.5. The present study demonstrates an adverse effect of reduced dietary Zn intake on glucose utilization in the genetically diabetic mouse, which occurred before any significant tissue Zn depletion became apparent.

Saponins Isolated from the Root of Panax notoginseng Showed Significant Anti-Diabetic Effects in KK-Ay Mice

2008 ◽  
Vol 36 (05) ◽  
pp. 939-951 ◽  
Author(s):  
Zhong-Hua Chen ◽  
Jie Li ◽  
Jie Liu ◽  
Yuan Zhao ◽  
Pu Zhang ◽  
...  
Keyword(s):  
Genetic Model ◽  
Day Treatment ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Chinese Herb ◽  
Clinical Importance ◽  
Resistance Index ◽  
Panax Notoginseng ◽  
Glucose Levels ◽  
Glomerular Lesions

Panax notoginseng, a well-known and commonly used traditional Chinese herb, has been used in China for six hundred years. Panax notoginseng Saponins (PNS) were extracted from the root of the plant. This is the first study on anti-hyperglycemic and anti-obese effects of PNS in genetic model mice. Additionally, the preventive effect on diabetic nephropathy was investigated. Animals received intraperitoneal injections of PNS 50 or 200 mg/kg daily. On day 12, 22 and 30, PNS-treated groups had significantly lower fasting blood glucose levels and smaller body weight incremental percentage. After a 12-day treatment, glucose tolerance of PNS groups were significantly improved; these indices in PNS-treated mice exhibited a dose-dependent improvement. Furthermore, on day 30, the serum insulin resistance index and triglyceride levels of PNS-treated groups decreased significantly, and the development of the mice glomerular lesions was prevented significantly. The results in this present paper indicate that PNS possesses anti-diabetes and anti-obese activities and may prove to be of clinical importance in improving the management of type 2 diabetes.

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.

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