scholarly journals Type 2 diabetes promotes cell centrosome amplification and the role of AKT-ROS-dependent signalling of ROCK1 and 14-3-3σ

2017 ◽  
Author(s):  
Pu Wang ◽  
Yu Cheng Lu ◽  
Jie Wang ◽  
Lan Wang ◽  
Hanry Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Palmitic Acid ◽  
High Glucose ◽  
Mononuclear Cells ◽  
Fasting Blood Glucose ◽  
Centrosome Amplification ◽  
Diabetic Patients ◽  
Ros Production ◽  
Akt Activation

AbstractType2 diabetes is associated with oxidative stress which can cause cell centrosome amplification. The study investigated centrosome amplification in type 2 diabetes and the underlying mechanisms. We found that centrosome amplification was increased in the peripheral blood mononuclear cells (PBMC) from the type 2 diabetic patients, which correlated with the levels of fasting blood glucose and HbA1c. High glucose, insulin and palmitic acid, alone or in combinations, induced ROS production and centrosome amplification. Together, they increased AKT activation as well as the expression, binding and centrosome translation of ROCK1 and 14-3-3σ. Results from further analyses showed that AKT-ROS-dependent upregulations of expression, binding and centrosome translocation of ROCK1 and 14-3-3σ was the molecular pathway underlying the centrosome amplification induced by high glucose, insulin and palmitic acid. Moreover, the increases in AKT activation and ROS production as well as expression, binding and centrosome distribution of ROCK1 and 14-3-3σ were confirmed in the PBMC from the patients with type 2 diabetes. In conclusion, our results show that type 2 diabetes promotes cell centrosome amplification, and suggest that the diabetic pathophysiological factors-activated AKT-ROS-dependent signalling of ROCK1 and 14-3-3σ is the underlying molecular mechanism.

scholarly journals Type 2 Diabetes Promotes Cell Centrosome Amplification via AKT-ROS-Dependent Signalling of ROCK1 and 14-3-3σ

2018 ◽  
Vol 47 (1) ◽  
pp. 356-367 ◽  
Author(s):  
Pu Wang ◽  
Yu Cheng Lu ◽  
Jie Wang ◽  
Lan Wang ◽  
Hanry Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Palmitic Acid ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Fasting Blood Glucose ◽  
Centrosome Amplification ◽  
Immunofluorescent Staining ◽  
Diabetic Patients

Background/Aims: Type 2 diabetes is associated with oxidative stress and DNA damage which can cause centrosome amplification. Thus, the study investigated centrosome amplification in type 2 diabetes and the underlying mechanisms. Methods: Centrosome numbers in human peripheral blood mononuclear blood cells (PBMC) from healthy subjects and patients with type 2 diabetes were compared to access the association between type 2 diabetes and centrosome amplification. Colon cancer cells were used to investigate the molecular mechanisms underlying the centrosome amplification triggered by high glucose, insulin and palmitic acid. Western blot analysis was used to quantify the level of protein and protein phosphorylation. Immunofluorescent staining was performed to detect centrosomes. ROS was quantified using flow cytometry technique. Transcriptpmic profiling was performed using Illumina HiSeqTM500 platform. Results: We found that centrosome amplification was increased PBMC from the type 2 diabetic patients, which correlated with the levels of fasting blood glucose and HbA1c. High glucose, insulin and palmitic acid, alone or in combinations, induced ROS production and centrosome amplification. Together, they increased AKT activation as well as the expression, binding and centrosome translation of ROCK1 and 14-3-3σ. Results from further analyses showed that AKT-ROS-dependent upregulations of expression, binding and centrosome translocation of ROCK1 and 14-3-3σ was the molecular pathway underlying the centrosome amplification in vitro triggered by high glucose, insulin and palmitic acid. Moreover, the key in vitro molecular signalling events activated by high glucose, insulin and palmitic acid were verified in PBMC from the patients with type 2 diabetes. Conclusion: Our results show that type 2 diabetes promotes cell centrosome amplification, and suggest that the diabetic pathophysiological factors-activated AKT-ROS-dependent signalling of ROCK1 and 14-3-3σ is the underlying molecular mechanism.

scholarly journals Resveratrol attenuates diabetes-associated cell centrosome amplification via inhibiting the PKCα-p38 to c-myc/c-jun pathway

2019 ◽  
Vol 52 (1) ◽  
pp. 72-83 ◽  
Author(s):  
Qigui Wu ◽  
Xiaoyu Chen ◽  
Qinju He ◽  
Lang Lang ◽  
Peng Xu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Palmitic Acid ◽  
Signaling Pathway ◽  
High Glucose ◽  
Mononuclear Cells ◽  
Centrosome Amplification ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels

Abstract Type 2 diabetes increases the risk for cancer. Centrosome amplification can initiate tumorigenesis. We have described that type 2 diabetes increases the centrosome amplification of peripheral blood mononuclear cells, with high glucose, insulin, and palmitic acid as the triggers, which suggests that centrosome amplification is a candidate biological mechanism linking diabetes to cancer. In this study, we aimed to further investigate the signaling pathways of the diabetes-associated centrosome amplification and to examine whether and how resveratrol inhibits the centrosome amplification. The results showed that treatment with high glucose, insulin, and palmitic acid, alone or in combination, could increase the protein levels of phospho-protein kinase C alpha (p-PKCα), phospho-p38 mitogen-activated protein kinases (p-p38), c-myc, and c-jun, as well as the mRNA levels of c-myc and c-jun. PKCα inhibitor could inhibit the treatment-induced increase in the protein levels of p-p38, c-myc, and c-jun. Inhibitor or siRNA of p38 was also able to inhibit the treatment-induced increase in the levels of p-p38, c-myc, and c-jun. Meanwhile, knockdown of c-myc or c-jun did not alter the treatment-induced increase in the phosphorylation of PKCα or p38. Importantly, inhibition of the phosphorylation of PKCα or p38 and knockdown of c-myc or c-jun could attenuate the centrosome amplification. In diabetic mice, the levels of p-PKCα, p-p38, c-myc, and c-jun were all increased in the colon tissues. Interestingly, resveratrol, but not metformin, was able to attenuate the treatment-induced increase in the levels of p-PKCα, p-p38, c-myc, and c-jun, as well as the centrosome amplification. In conclusion, our results suggest that PKCα-p38 to c-myc/c-jun is the signaling pathway of the diabetes-associated centrosome amplification, and resveratrol attenuates the centrosome amplification by inhibiting this signaling pathway.

Prevalence of Toenail Onychomycosis in Patients with Type 2 Diabetes Mellitus and Evaluation of Risk Factors

2011 ◽  
Vol 101 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Aynur Gulcan ◽  
Erim Gulcan ◽  
Sukru Oksuz ◽  
Idris Sahin ◽  
Demet Kaya
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Fasting Blood Glucose ◽  
Diabetic Patients ◽  
Essential Components ◽  
Patients With Diabetes ◽  
Epidemiologic Risk

Background: We sought to determine the frequency of toenail onychomycosis in diabetic patients, to identify the causative agents, and to evaluate the epidemiologic risk factors. Methods: Data regarding patients’ diabetic characteristics were recorded by the attending internal medicine clinician. Clinical examinations of patients’ toenails were performed by a dermatologist, and specimens were collected from the nails to establish the onycomycotic abnormality. All of the specimens were analyzed by direct microscopy and culture. Results: Of 321 patients with type 2 diabetes mellitus, clinical onychomycosis was diagnosed in 162; 41 of those diagnoses were confirmed mycologically. Of the isolated fungi, 23 were yeasts and 18 were dermatophytes. Significant correlations were found between the frequency of onychomycosis and retinopathy, neuropathy, obesity, family history, and duration of diabetes. However, no correlation was found with sex, age, educational level, occupation, area of residence, levels of hemoglobin A1c and fasting blood glucose, and nephropathy. The most frequently isolated agents from clinical specimens were yeasts. Conclusions: Long-term control of glycemia to prevent chronic complications and obesity and to promote education about the importance of foot and nail care should be essential components in preventing onychomycosis and its potential complications, such as secondary foot lesions, in patients with diabetes mellitus. (J Am Podiatr Med Assoc 101(1): 49–54, 2011)

scholarly journals Fenofibrate decreased microalbuminuria in the type 2 diabetes patients with hypertriglyceridemia

2020 ◽  
Author(s):  
Xiaomeng Sun ◽  
Jia Liu ◽  
Guang Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Treatment Group ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Diabetic Patients ◽  
Fenofibrate Treatment

Abstract Background: This study was to research the efficacy of fenofibrate in the treatment of microalbuminuria in the patients with type 2 diabetes mellitus (T2DM) and hypertriglyceridemia. Methods: Type 2 diabetic patients (56) with microalbuminuria and hypertriglyceridemia aged 30 to 75 were randomly divided into the fenofibrate treatment group(n=28) and the control group (n=28) for 180 days. Urinary microalbumin /creatinine ratio (UACR) and other metabolic parameters were compared at baseline, during treatment and after treatment. Results: After 180 days, the reduction of levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in two groups were no differences. In treatment group, uric acid (UA) (296.42 ± 56.41 vs 372.46 ± 72.78), triglyceride (TG) [1.51(1.17, 2.06) vs 3.04(2.21, 3.29)], and UACR [36.45 (15.78,102.41) vs 129.00 (53.00, 226.25)] were significantly decreased compared with the baseline. The high-density lipoprotein cholesterol (HDL-C) levels were significantly increased (1.22 ± 0.26 vs 1.09 ± 0.24) compared with the baseline. The decrease in UACR [-44.05(-179.47, -12.16) vs -8.15(-59.69, 41.94)]in treatment group was significantly higher compared with the control group. The decrease in UACR was positively associated with the decreases in TG ( r = 0.447, P = 0.042) and UA ( r = 0.478, P = 0.024) after fenofibrate treatment. Conclusion: In the patients with hypertriglyceridemia and type 2 diabetes mellitus, fenofibrate can improve microalbuminuria and do not increase the deterioration of glomerular filtration rate

scholarly journals Correlation between glycated hemoglobin HbA1c and serum lipid profile in patients with type 2 diabetes

2021 ◽  
pp. 14-18
Author(s):  
Asmaa Alboueishi
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Glucose ◽  
Serum Lipid ◽  
Clinical Laboratory ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Diabetic Patients

Background: Hyperlipidemia is a common risk factor for diabetes that leads to cardiovascular disease, one of the causes of death of diabetic patients. Theaimof this study was to investigate the association between HbA1c levels and serum lipids in Libyan patients withtype 2 diabetes. Material and methods: The study was conducted in 2019 on 325 patients (174 males, 151 females) with type 2 diabetes referred to a private clinical laboratory in Tripoli, Libya. Blood samples were collected for measurement of HbA1c, fasting blood glucose and serum lipid concentrations. Diabetes was defined according to the American Diabetes Association criteria.The data were analyzed using an independent t-test and Pearson’scorrelation test.Results: The ages of the patients ranged from 40 to 83 years, with a mean of 51.52 ± 14.32 years SD. No significant correlation between HbA1c and age was noted (r=0.011, p=0.063). There was a significant positive correlation betweenHbA1c level and fasting blood glucose (r =0.641, p=0.000), low-density lipoprotein (r = 0.240, p = 0.000), total cholesterol (r = 0.223, p = 0.000) and triglycerides(r=0.140,p 0.067). The correlation between HbA1c and high-density lipoprotein-C was negative but not significant (r= -0.088, p = 0.123). Conclusion: HbA1c could be used as a predictor of dyslipidemia and thus it may serve as anindicator of the development of cardiovascular disease in patients with type-2 diabetes mellitus.

scholarly journals miR-145 improves metabolic inflammatory disease through multiple pathways

2019 ◽  
Vol 12 (2) ◽  
pp. 152-162 ◽  
Author(s):  
Min He ◽  
Nan Wu ◽  
Man Cheong Leong ◽  
Weiwei Zhang ◽  
Zi Ye ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Strategy ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Diabetic Patients ◽  
Peripheral Blood Mononuclear ◽  
Reduced Body ◽  
Type 2 Diabetics ◽  
Induced Apoptosis

Abstract Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes, yet the mechanisms are not completely understood. Here, we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control. miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics. LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels. Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice. Conversely, lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration, reduced body weight, and improved glucose metabolism in db/db mice. And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE−/− mice. Both OPG and KLF5 were targets of miR-145. miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5. miR-145 also suppressed NF-κB activation by targeting OPG and KLF5. Our findings provide an association of the environment with the progress of metabolic disorders. Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.

scholarly journals Nocturnal Glucose Metabolism after Bedtime Injection of Insulin Glargine or Neutral Protamine Hagedorn Insulin in Patients with Type 2 Diabetes

2008 ◽  
Vol 93 (10) ◽  
pp. 3839-3846 ◽  
Author(s):  
Thomas Linn ◽  
Britta Fischer ◽  
Nedim Soydan ◽  
Michael Eckhard ◽  
Julia Ehl ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
Fasting Blood Glucose ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Nph Insulin ◽  
Double Blind ◽  
Glucose Levels ◽  
Neutral Protamine Hagedorn

Aims/Hypothesis: Insulin glargine is a long-acting human insulin analog often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycemic events compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning. Methods: In 10 type 2 diabetic patients, euglycemic clamps were performed, including [6,6′]2H2 glucose, to study the rate of disappearance (Rd) and endogenous production (EGP) of glucose during the night. On separate days at bedtime (2200 h), patients received a sc injection of insulin glargine, NPH insulin, or saline in a randomized, double-blind fashion. Results: Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared with insulin glargine. By contrast, in the morning, insulin glargine was more effective, increasing Rd by 5.8 μmol/kg−1·min−1 (95% confidence interval 4.7–6.9) and reducing EGP −5.7 (−5.0 to −6.4) compared with NPH insulin. Nearly 80% of the glucose lowering effect in the morning was due to insulin glargine’s reduction of EGP. Its injection was associated with one-third lower morning glucagon levels compared with NPH insulin (P = 0.021). Conclusion/Interpretation: Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin.

scholarly journals Comparison of Metformin and Repaglinide Monotherapy in the Treatment of New Onset Type 2 Diabetes Mellitus in China

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
J. Ma ◽  
L. Y. Liu ◽  
P. H. Wu ◽  
Y. Liao ◽  
T. Tao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Glycated Haemoglobin ◽  
Diabetic Patients ◽  
Newly Diagnosed ◽  
Type 2 Diabetic Patients ◽  
New Onset

Objective. This study was designed to compare the effects of metformin and repaglinide on the fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in newly diagnosed type 2 diabetes in China.Methods. A total of 107 newly diagnosed type 2 diabetic patients (46 women and 61 men) participated in the study. All patients received 3-month treatment of metformin or repaglinide. Fasting blood glucose and HbA1c were determined at baseline and at the end of the 3-month of treatment.Results. FPG and HbA1c decreased in both metformin and repaglinide groups after 3 months treatment (P<0.01). The reduction of HbA1c was significantly greater in the repaglinide group(P<0.01). Metformin decreases fasting insulin concentration and HOMA-IR(P<0.01), and repaglinide improves HOMA-β  (P<0.01). Triglycerides (TG) were reduced in both groups(P<0.01in metformin group;P<0.05in repaglinide group), but total cholesterol (TC) and low-density lipoprotein (LDL) were decreased only after metformin treatment(P<0.05).Conclusions. Both repaglinide and metformin were effective in glycaemic control in new onset patients with type 2 diabetes in China. Repaglinide had no effect on insulin sensitivity, but it improvedβ-cell function.

scholarly journals The association between Gastric Bacterial Infection and Low Level of Vitamin D among Patients with type 2 Diabetes Mellitus

2021 ◽  
Vol 2 (01) ◽  
pp. 38-46
Author(s):  
Sarah T. Al-Mofarji ◽  
Haider .K. Hussien ◽  
Nadira Salman Mohamed ◽  
Sundus Fadhil Hantoosh ◽  
Mohammed Khudier Abass ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Fasting Blood Glucose ◽  
Diabetic Group ◽  
Diabetic Patients ◽  
Vitamin D Levels ◽  
H Pylori

Objectives: The present research aimed to find an association between infection by  Helicobacter pylori and vitamin D deficiency in type 2 diabetes mellitus among Iraqi individuals attending Al-Yarmouk Teaching Hospital. Methods: According to fasting blood glucose,  the samples were divided into a non-diabetic group with ten diabetic individuals and a diabetic group with thirty individuals. Results: The anti-H. Pylori (IgG) levels were 86.77± 58.62 NTU/µL in diabetic patients compared with 10.12 ± 7.40 NTU/µL in non- diabetic group. Vitamin D levels were decreased significantly in infected patients compared to non-infected subjects. Conclusion: The H pylori-infected patients have recorded the lowest level of vitamin D than non-infected individuals.

scholarly journals Factors Associated with Glycaemic Control among Diabetic Patients Managed at an Urban Hospital in Hanoi, Vietnam

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Luu Quang Thuy ◽  
Hoang Thi Phuong Nam ◽  
Tran Thi Ha An ◽  
Bui Van San ◽  
Tran Nguyen Ngoc ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycaemic Control ◽  
Associated Factors ◽  
Fasting Blood Glucose ◽  
Management Strategies ◽  
Diabetic Patients ◽  
Urban Hospital ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes (T2DM) epidemic is rising in Vietnam. Identifying associated factors with glycaemic control in patients with T2DM is vital to improve treatment outcomes. This study is aimed at examining the uncontrolled glycaemic level of patients with type 2 diabetes (T2DM) at an urban hospital in Hanoi, Vietnam, and determining associated factors. An observational longitudinal cohort survey was performed among T2DM patients. Glycaemic control was evaluated by using the HbA 1 c   level ≥ 6.5 % or fasting blood   glucose   level ≥ 7.5   g / mmol . Information about sociodemographic, clinical, and behavioral characteristics was collected. Multivariate mixed-effects logistic regression was employed to identify associated factors with control glycaemic level conditions. Among 189 T2DM patients, 70.4% had an uncontrolled glycaemic level. A higher number of comorbidities were associated with a lower likelihood of having uncontrolled glycaemic levels ( OR = 0.71 , p < 0.001 , 95 % CI = 0.52 − 0.98 ). Meanwhile, a higher body mass index ( OR = 1.15 , p < 0.05 , 95 % CI = 1.02 − 1.29 ), higher initial HbA1C ( OR = 3.75 , p < 0.01 , 95 % CI = 2.59 − 5.44 ), and higher initial fasting blood glucose levels ( OR = 1.57 , p < 0.01 , 95 % CI = 1.29 − 1.90 ) were positively associated with a higher risk of uncontrolled glycaemic levels. This study reveals that poor glycaemic control was common among T2DM patients in the urban hospital in Vietnam. Findings underlined the need for appropriate management strategies to control glycaemic levels and weight in this population.

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