Suppressive Activity of the Fruit of Momordica charantia with Exercise on Blood Glucose in Type 2 Diabetic Mice

Background: Type 2 diabetes (T2D) is the most common form of diabetes and accounts for 90-95% of all existing diabetic cases. The main etiologies of T2D include insulin resistance in target tissues, insufficient secretion of insulin and subsequent decline of pancreatic β-cell function. Recently, many studies have suggested that adipose – derived stem cells (ASCs) were potential to alleviate insulin resistance and hyperglycemia and promote the islets repair. In this study, ASCs were hypothesized that they could have ameliorative effects on type 2 diabetic mice. Methods: Type 2 diabetic mice were induced by a combination of high-fat diet and injection of STZ 100 mg/kg and NA 120 mg/kg. Thereafter, two doses of 106 human ASCs were transplanted 2 week interval into each mouse via the tail vein. The mice were monitored health condition, rate of mortaity, body weight, consumption of food and water, blood glucose level, serum insulin level and histological structure of pancreatic islets. Results: Our results indicated that the ASC-treated mice expressed improved condition in comparision with non-treated diabetic mice. The consumption of food and water as well as the blood glucose level decreased. Simultaneously, ASC transplantation improved the impaired glucose tolerance and insulin tolerance in T2D mice. Besides, the total cholesterol have significantly decreased. Conclusion: it is suggested that human ASCs infusion is safe and effective for type 2 diabetes mellitus in mice regarding the improved glucose metabolism and insulin resistance.

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Abstract 279: Stromal Cell-derived Factor-1 Prevents From Diabetic Cardiomyopathy via Cxcr7/ampk-mediated Nrf2 Activation in Type 2 Diabetic Mice

Circulation Research ◽

10.1161/res.119.suppl_1.279 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Shudong Wang ◽

Junlian Gu ◽

Xiaoqing Yan ◽

Jing Chen ◽

Jun Chen ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Cardiac Function ◽

Stromal Cell ◽

Normal Diet ◽

Diabetic Mice ◽

Nrf2 Activation ◽

Stromal Cell Derived Factor ◽

Type 2 Diabetic

We have demonstrated that stromal cell-derived factor 1(SDF-1) protects against palmitate-induced cardiac cell death via CXCR7-mediated activation of AMPK signaling (Diabetes 62:2545-2558, 2013). Whether SDF-1 prevents diabetic cardiomyopathy (DCM) and what the underlying mechanism has not been addressed. Here we evaluated the prevention of SDF-1 from DCM in a high fat diet plus streptozotocin (HFD/STZ)-induced type 2 diabetic model in C57BL/6J mice. After 1 month on HFD, the HFD-fed mice were injected with one low dose STZ (100mg/kg body weight, ip). Five days after STZ injection, mice with blood glucose levels ≥250 mg/dl were defined as diabetic. In parallel, the age-matched normal diet-fed mice injected with a same volume of vehicle were used as control. After onset of diabetes, the mice were maintained on HFD or normal diet for another 4 months with or without SDF-1 treatment. Then cardiac function was assayed again, and the mice were sacrificed and cardiac tissue collected for cardiomyopathic index assay. We found that 1 month HFD feeding induced a significant insulin resistance without effect on cardiac function, but continued HFD feeding after STZ injection significantly increased insulin resistance and blood glucose, as well as blood insulin, triglyceride and cholesterol levels. Furthermore, HFD/STZT significantly impaired cardiac function, which were accompanied by increased cardiac inflammation, oxidative stress and fibrotic remodeling. Treatment with SDF-1 dose-dependently prevented diabetes-induced cardiac dysfunction, inflammation and remodeling, but without significant effects on the above mentioned other pathophysiological changes. Mechanistic study demonstrated that diabetes significantly inhibited the function of AMPK and Nrf2, and the expression of CXCR7, but not CXCR4; while treatment with SDF-1 significantly preserved AMPK and Nrf2 function and CXCR7 expression. Knockout CXCR4 did not affect SDF-1 preservation of AMPK and Nrf2 function, but SiRNA knockdown of AMPK resulted in blockade of SDF-1 preservation of Nrf2 function. These results indicate that SDF-1 prevents from DCM via CXCR7/AMPK-mediated Nrf2 activation in type 2 diabetic mice.

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Effect of Momordica charantia on Adenosine Monophosphate-activated Protein Kinase in Genetically Type 2 Diabetic Mice Muscle

JOURNAL OF HEALTH SCIENCE ◽

10.1248/jhs.55.805 ◽

2009 ◽

Vol 55 (5) ◽

pp. 805-808 ◽

Cited By ~ 2

Author(s):

Toshihiro Miura ◽

Takanori Kawata ◽

Satoshi Takagi ◽

Mai Nanpei ◽

Haruka Nakao ◽

...

Keyword(s):

Protein Kinase ◽

Adenosine Monophosphate ◽

Momordica Charantia ◽

Diabetic Mice ◽

Type 2 Diabetic

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Drinking Watermelon Juice Shift the Gut Microbiome in Diabetic Mice (P20-025-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz040.p20-025-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Siau Yen Wong ◽

Lei Wu ◽

Peiran Lu ◽

Babajide Ojo ◽

Minghua Tang ◽

...

Keyword(s):

Blood Glucose ◽

Gut Microbiome ◽

Tap Water ◽

Fasting Blood Glucose ◽

Chow Diet ◽

Diabetic Mice ◽

Watermelon Juice ◽

Type 2 Diabetic

Abstract Objectives Watermelon is a delicious and healthy fruit that contains low calories and is rich in carotenoids, vitamin A, vitamin C, citrulline, and other bioactive compounds. The health benefits of watermelon in diabetes are poorly understood. In the current study, we sought to determine the effects of watermelon juice on gut microbiome profile and blood glucose management in type 1 and type 2 diabetic mice. Methods Six-week-old male C57BL/6 J wild type (WT), db/db type 2 diabetic (db/db), and streptozocin (STZ)-induced type 1 (STZ) diabetic mice were fed a chow diet and given 50% or 100% watermelon juice or tape water during night cycle for 8 weeks. At the termination of the study, mice were fasted for 3 hrs prior to euthanization. Blood, cecal contents, and other tissues were collected for laboratory assessments. Plasma metabolic parameters and pro-inflammatory cytokines were monitored by a clinical analyzer and ELISA, respectively. Cecal microbiome was profiled by 16S rRNA sequencing and followed by bioinformatic analysis. Results Consumption of watermelon juice significantly lowered fasting blood glucose levels in both diabetic mouse models. The fasting insulin level was significantly decreased in db/db consuming watermelon juice, though it was undetectable in STZ mice, with or without watermelon juice. Drinking watermelon juice tremendously changed the gut microbiome composition. At the phylum level, the Firmicutes/Bacteroidetes ratio was significantly associated with genotype (e.g., WT vs STZ vs db/db) and diet (e.g., watermelon juice vs tap water). At the genus level, abundances of Ruminiclostridium_9, Parasutterella, and Clostridium_sensu_stricto_1 were increased in STZ mice with watermelon, and abundances of Oscillibacter and Ruminiclostridium were decreased in db/db mice with watermelon. Watermelon juice induced gut microbiome compositional changes also occurred at the species level. Conclusions Watermelon juice intervention causes a decrease in blood glucose level and shifts of the gut microbiome in both type 1 and type 2 mice. Funding Sources National watermelon board grant.

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The plasma 5′-AMP acts as a potential upstream regulator of hyperglycemia in type 2 diabetic mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00424.2011 ◽

2012 ◽

Vol 302 (3) ◽

pp. E325-E333 ◽

Cited By ~ 11

Author(s):

Ying Zhang ◽

Zhongqiu Wang ◽

Yue Zhao ◽

Ming Zhao ◽

Shiming Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Adenosine Monophosphate ◽

Plasma Free Fatty Acid ◽

Hepatic Glycogen ◽

Diabetic Mice ◽

Wild Type ◽

Upstream Regulator ◽

Type 2 Diabetic

Increased plasma free fatty acid (FFA) level is a hallmark of type 2 diabetes. However, the underlying molecular basis for FFA-caused hyperglycemia remains unclear. Here we identified plasma 5′-adenosine monophosphate (pAMP) markedly elevated in the plasma of type 2 diabetic mice. High levels of FFAs induced damage in vein endothelial cells and contributed to an increase in pAMP. Administration of synthetic 5′-AMP caused hyperglycemia and impaired insulin action in lean wild-type mice. 5′-AMP elevated blood glucose in mice deficient in adenosine receptors with equal efficiency as wild-type mice. The function of pAMP was initiated by the elevation of cellular adenosine levels, directly stimulating G-6-Pase enzyme activity, attenuating insulin-dependent GLUT4 translocation in skeletal muscle, and displaying a rapid and steep increase in blood glucose and a decrease in hepatic glycogen level. It was followed by an increase in the gene expression of hepatic Foxo1 and its targeting gene Pepck and G6Pase, which was similar to diabetic phenotype in db/db mice. Our results suggest that pAMP is a potential upstream regulator of hyperglycemia in type 2 diabetes.

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GLP-1 Gene-Modified Human Umbilical Cord Mesenchymal Stem Cell Line Improves Blood Glucose Level in Type 2 Diabetic Mice

Stem Cells International ◽

10.1155/2019/4961865 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Ying Chang ◽

Mingxin Dong ◽

Yan Wang ◽

Haotian Yu ◽

Chengbiao Sun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Stem Cells ◽

Blood Glucose ◽

Cell Line ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Diabetic Mice ◽

Type 2 Diabetic

Type 2 diabetes constitutes a serious threat to the health of patients, but there is currently no ideal treatment in the clinic. Glucagon-like peptide-1 and human umbilical cord mesenchymal stem cells have been confirmed to have antidiabetic effects, but both of them have certain defects in the process of antidiabetes, which cannot meet the need of clinical treatment. We hypothesized that human umbilical cord mesenchymal stem cells can be used as a vector to construct a novel cell line that expresses GLP-1 in vivo for a long time. And this cell strain results in lowering blood glucose in type 2 diabetic mice. The results showed that after 3 weeks of intramuscular injection of the new cell line, the fasting blood glucose of type 2 diabetic mice returned to the normal range, and the hypoglycemic effect was maintained within 3 weeks after putting an end to the drug. At the same time, during the administration, the mice lost weight, the food intake decreased, the half-life of GLP-1 in the body prolonged, the IR reduced, and the pancreatic function recovered. The results of this study indicate that the novel cell line can prolong the half-life of GLP-1 in vivo and effectively lower blood sugar, which is a feasible method to improve type 2 diabetes.

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