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

2012 ◽  
Vol 302 (3) ◽  
pp. E325-E333 ◽  
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.

scholarly journals ID: 1080 Adipose-derived stem cells alleviate glucose tolerance in type 2 diabetic mouse

2017 ◽  
Vol 4 (S) ◽  
pp. 166
Author(s):  
Anh Nguyen Tu Bui ◽  
Cong Le Thanh Nguyen ◽  
Anh Thi Minh Nguyen ◽  
Nhat Chau Truong ◽  
Ngoc Kim Phan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Stem Cells ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Human Ascs ◽  
Type 2 Diabetic

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.

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

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.

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

2020 ◽  
Vol 45 (4) ◽  
pp. 397-404
Author(s):  
Tugba Gurpinar Çavuşoğlu ◽  
Ertan Darıverenli ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Cevval Ulman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Insulin Levels ◽  
Type 2 Diabetic

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.

scholarly journals Study on the prevalence of dyslipidemia in type 2 diabetes mellitus

2019 ◽  
Vol 6 (3) ◽  
pp. 786
Author(s):  
Eda Dayakar ◽  
C. Sathya Sree ◽  
E. Sanjay
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Type 2 Diabetic

Background: Diabetes mellitus is a common health problem globally. Dyslipidaemia is a major risk factor to develop cardiovascular disease in diabetics. They present study was undertaken to find out the prevalence of dyslipidaemia in type 2 diabetic patients.Methods: The present study was a cross sectional study consisting of 46 (23 male and 23 female) known type 2 diabetes mellitus patients. Age, gender, duration of diabetes, body mass index (BMI) was recorder in all the diabetic patients.  Fasting blood glucose levels, total cholesterol, triglycerides, HDL, LDL, VLDL levels were measured using standard methods and recorded.Results: The average total cholesterol, triglycerides, LDL, HDL and VLDL were 200±42mg/dl, 169.62±89.79mg/dl, 132.45±36.38mg/dl,39.1±16.6mg/dl and 35.85±17.09mg/dl respectively. The incidence of occurrence of hypercholesterolemia was 58.6% and hypertriglyceridemia 36.9%. Increased levels of LDL were observed in 30 (65.2%) patients and reduced HDL was observed in 43 (93.4%) patients. The incidence rate of dyslipidaemia was higher in female diabetic patients when compared to male diabetic patients.Conclusions: Awareness on the dyslipidaemia and its risk factors should be provided to the type 2 diabetic patients as they are more prone to get cardiovascular disease and lipid profile also should be monitored regularly along with blood glucose levels.

scholarly journals Protective Effects of Konjac and Inulin Extracts on Type 1 and Type 2 Diabetes

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Tianle Gao ◽  
Yue Jiao ◽  
Yang Liu ◽  
Tao Li ◽  
Zhiguo Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Dose Group ◽  
Vehicle Control ◽  
Continuous Treatment ◽  
High Risk Population ◽  
Wild Type ◽  
Group A

Objective. The present study was designed to determine whether konjac and inulin extracts or their combination, konjac-inulin (KI) composition, as diet supplementary, can exert beneficial effects against type 1 diabetes and type 2 diabetes using animal models. Methods. A total of 60 diabetic (type 1) rats induced by streptozotocin (STZ) were randomly assigned to five groups: vehicle control (STZ group), KI combination at low dose group (KI-L group), KI combination at medium dose group (KI-M group), KI combination at high dose group (KI-H group), konjac extract group (konjac group), and inulin extract group (inulin group). A sham group (without STZ) was also included. Levels of blood glucose were monitored at each week. After continuous treatment of each diet for 24 days, a glucose tolerance test was performed. After 28 days of treatment, plasma biochemical indicators including glycated serum proteins, total cholesterol, and triglycerides were measured and immunohistochemistry staining of the rat pancreas was performed, to study the insulin expressions. Type 2 diabetes was developed in db/db mice. A total of 28 db/db mice were divided into 4 groups: vehicle control (db/db group), KI composition group (KI group), konjac extract group (konjac group), and inulin extract group (inulin group). A wild-type control group (wild-type group) for db/db mice was also included. Levels of blood glucose, body weight, and blood triglycerides were monitored at each week. Results. Daily use of the KI composition significantly decreased levels of blood glucose and blood triglycerides, as well as improved the insulin production in islets or reduced development of obesity in STZ-induced diabetic rats or in db/db mice. Such effects from KI composition were better than single ingredient of konjac or inulin extract. Conclusion. The results of this study suggest that daily use of KI composition has a protective role on type 1 and 2 diabetes and provided experimental basis for further development of KI composition as a food supplement for diabetic or diabetic high-risk population.

scholarly journals Consumption of Whole Eggs Promotes Insulin Sensitivity in Db/db Mice (OR34-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Peiran Lu ◽  
Lei Wu ◽  
Xin Guo ◽  
Siau Yen Wong ◽  
Stephen Clarke ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Cholesterol Synthesis ◽  
Respiratory Activity ◽  
High Cholesterol ◽  
Egg Consumption ◽  
Type 2 Diabetic ◽  
Mitochondrial Respiratory Activity

Abstract Objectives Chicken eggs have a high nutrient density. Some country guidelines recommend that people with type 2 diabetes (T2D) limit their consumption of eggs due to its high cholesterol content. However, several clinical studies showed that egg intake is associated with a lower risk of type 2 diabetes. In the current study, we sought to explore whether egg consumption improves insulin sensitivity and subsequent blood glucose management in type 2 diabetic db/db mice. Methods Six-week-old male db/db mice were fed a low-fat diet (LFD, 10 kCal % from fat) or LFD supplemented with 1% whole eggs (Egg) for 8 weeks. At the termination of the study, mice were fasted for 3 hrs prior to euthanization. Blood and other tissues were collected for laboratory assessments. Plasma metabolic parameters and pro-inflammatory cytokines were monitored by a clinical analyzer and ELISA, respectively. Hepatic and skeletal muscle mitochondrial respiratory activity was assessed by a Seahorse XFe Analyzer. Hepatic gene expression was analyzed by transcriptomics and confirmed by real-time PCR and/or Western blot. Results Egg consumption significantly increased body weight gain, lowered fasting blood glucose, insulin, and IL-6 levels, and elevated total cholesterol, HDL, LDL, and GLP-1 levels. Only the basal mitochondrial respiratory activity was decreased, and the complex II respiratory activity was increased in gastrocnemius muscles in mice fed Egg. Hepatic mitochondrial activity was not altered by diet. Mechanistically, transcriptomics results revealed that hepatic genes involved in enhanced insulin sensitivity were highly expressed, but genes in endogenous cholesterol synthesis were significantly suppressed after egg consumption. Conclusions The results suggest that egg consumption is beneficial to blood glucose control in type 2 diabetic mice. Type 2 diabetic animal could manage the cholesterol level through suppression of de novo cholesterol synthesis when consuming a high cholesterol diet, e.g., egg diet. Funding Sources National egg nutrition center grant USDA NIFA grant

scholarly journals Reduction of islet pyruvate carboxylase activity might be related to the development of type 2 diabetes mellitus in Agouti-K mice

2009 ◽  
Vol 204 (2) ◽  
pp. 143-152 ◽  
Author(s):  
J Han ◽  
Y Q Liu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Protein Level ◽  
Pyruvate Carboxylase ◽  
Β Cell ◽  
Cell Adaptation ◽  
Type 2 Diabetic

Pyruvate carboxylase (PC) activity is enhanced in the islets of obese rats, but it is reduced in the islets of type 2 diabetic rats, suggesting the importance of PC in β-cell adaptation to insulin resistance as well as the possibility that PC reduction might lead to hyperglycemia. However, the causality is currently unknown. We used obese Agouti mice (AyL) as a model to show enhanced β-cell adaptation, and type 2 diabetic db/db mice as a model to show severe β-cell failure. After comparison of the two models, a less severe type 2 diabetic Agouti-K (AyK) mouse model was used to show the changes in islet PC activity during the development of type 2 diabetes mellitus (T2DM). AyK mice were separated into two groups: mildly (AyK-M, blood glucose <250 mg/dl) and severely (AyK-S, blood glucose >250 mg/dl) hyperglycemic. Islet PC activity, but not protein level, was increased 1.7-fold in AyK-M mice; in AyK-S mice, islet PC activity and protein level were reduced. All other changes including insulin secretion and islet morphology in AyK-M mice were similar to those observed in AyL mice, but they were worse in AyK-S mice where these parameters closely matched those in db/db mice. In 2-day treated islets, PC activity was inhibited by high glucose but not by palmitate. Our findings suggest that islet PC might play a role in the development of T2DM where reduction of PC activity might be a consequence of mild hyperglycemia and a cause for severe hyperglycemia.

scholarly journals MiR-27b augments bone marrow progenitor cell survival via suppressing the mitochondrial apoptotic pathway in Type 2 diabetes

2017 ◽  
Vol 313 (4) ◽  
pp. E391-E401 ◽  
Author(s):  
Hainan Li ◽  
Jenny Liu ◽  
Yihan Wang ◽  
Zhiyao Fu ◽  
Maik Hüttemann ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Cell Therapy ◽  
Progenitor Cell ◽  
Diabetic Mice ◽  
Tissue Repair And Regeneration ◽  
Autologous Cell ◽  
Autologous Cell Therapy ◽  
Type 2 Diabetic

Bone marrow-derived progenitor cells (BMPCs) are potential candidates for autologous cell therapy in tissue repair and regeneration because of their high angiogenic potential. However, increased progenitor cell apoptosis in diabetes directly limits their success in the clinic. MicroRNAs are endogenous noncoding RNAs that regulate gene expression at the posttranscriptional level, but their roles in BMPC-mediated angiogenesis are incompletely understood. In the present study, we tested the hypothesis that the proangiogenic miR-27b inhibits BMPC apoptosis in Type 2 diabetes. Bone marrow-derived EPCs from adult male Type 2 diabetic db/db mice and their normal littermates db/+ mice were used. MiR-27b expression (real-time PCR) in EPCs was decreased after 24 h of exposure to methylglyoxal (MGO) or oxidized low-density lipoprotein but not high glucose, advanced glycation end products, the reactive oxygen species generator LY83583, or H2O2. The increase in BMPC apoptosis in the diabetic mice was rescued following transfection with a miR-27b mimic, and the increased apoptosis induced by MGO was also rescued by the miR-27b mimic. p53 protein expression and the Bax/Bcl-2 ratio in EPCs (Western blot analyses) were significantly higher in db/db mice, both of which were suppressed by miR-27b. Furthermore, mitochondrial respiration, as measured by oxygen consumption rate, was enhanced by miR-27b in diabetic BMPCs, with concomitant decrease of mitochondrial Bax/Bcl-2 ratio. The 3′ UTR binding assays revealed that both Bax, and its activator RUNX1, were direct targets of miR-27b, suggesting that miR-27b inhibits Bax expression in both direct and indirect manners. miR-27b prevents EPC apoptosis in Type 2 diabetic mice, at least in part, by suppressing p53 and the Bax/Bcl-2 ratio. These findings may provide a mechanistic basis for rescuing BMPC dysfunction in diabetes for successful autologous cell therapy.

scholarly journals Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes

2012 ◽  
Vol 216 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Lucy M Hinder ◽  
Anuradha Vivekanandan-Giri ◽  
Lisa L McLean ◽  
Subramaniam Pennathur ◽  
Eva L Feldman
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Sural Nerve ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted liquid chromatography–tandem mass spectrometry (LC/MS/MS) to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve, and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Leprdb;db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, and lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve, and DRG from diabetic mice. Utilizing LC/electrospray ionization/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids) indb/dbtissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerves to rely on truncated TCA cycle metabolism in the type 2 diabetes environment.

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