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 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 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.

scholarly journals Molecular mechanisms and the vital roles of resistin, TLR 4, and NF-κB in treating type 2 diabetic complications

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Venkataiah Gudise ◽  
Bimalendu Chowdhury
Keyword(s):  
Type 2 Diabetes ◽  
Effective Treatment ◽  
Diabetic Complications ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Rapid Progression ◽  
Main Body

Abstract Background Type 2 diabetes in obese (≥ 25 and ≥ 30 kg/m2) patients is the foremost cause of cardiovascular complications like stroke, osteoarthritis, cancers (endometrial, breast, ovarian, liver, kidney, colon, and prostate), and vascular complications like diabetic neuropathy, diabetic and retinopathy, and diabetic nephropathy. It is recognized as a global burden disorder with high prevalence in middle-income nations which might lead to a double burden on health care professionals. Hence, this review emphasizes on understanding the complexity and vital signaling tracts involved in diabetic complications for effective treatment. Main body Type 2 diabetes in overweight patients induces the creation of specific ROS that further leads to changes in cellular proliferation, hypothalamus, and fringe. The resistin, TLR4, and NF-κB signalings are mainly involved in the progression of central and fringe changes such as insulin resistance and inflammation in diabetic patients. The overexpression of these signals might lead to the rapid progression of diabetic vascular complications induced by the release of proinflammatory cytokines, chemokines, interleukins, and cyclooxygenase-mediated chemicals. Until now, there has been no curative treatment for diabetes. Therefore, to effectively treat complications of type 2 diabetes, the researchers need to concentrate on the molecular mechanisms and important signaling tracts involved. Conclusion In this review, we suggested the molecular mechanism of STZ-HFD induced type 2 diabetes and the vital roles of resistin, TLR4, and NF-κB signalings in central, fringe changes, and development diabetic complications for its effective treatment. Graphical abstract

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 Effect of Agmatine on Non-Alcoholic Fatty Liver Disease Induced by Type 2 Diabetes in Rats

2021 ◽  
pp. 127-134
Author(s):  
Samar F. Miski ◽  
Mai A. Alim A. Sattar Ahmad ◽  
Ahmed Esmat
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Histopathological Examination ◽  
Fasting Blood Glucose ◽  
Serum Levels ◽  
Current Data ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Alcoholic Fatty Liver

Aim: To determine the potential hepatoprotective effect of Agmatine (AGM) on NAFLD-induced by Type 2 diabetes mellitus (T2DM) in rats. Study design:  Forty male Wistar rats weighing from (200 -250 g) were distributed at random into five groups (8 rats per group): group 1 as control; group 2 as untreated-T2DM; groups 3 & 4 as T2DM cotreated with AGM (40 & 80 mg/kg/d), while group 5 T2DM cotreated with Silymarin (100 mg/kg/d). Place and duration of study: Department of Pharmacology, Faculty of Medicine, king Abdul-Aziz University; between October 2020 and January 2021. Methodology: A rat model of T2DM with NAFLD complication was established by feeding rats with 10% fructose in drinking water and intraperitoneally injecting them with a single low dose of streptozotocin (STZ) (45mg/kg). The fasting blood glucose was detected, serum levels of hepatic biomarkers were all assessed. Moreover, histopathological examination was performed by hematoxylin and eosin (H&E) staining. Results: STZ induced T2DM in rats causes a significant (p<0.05, n=8) rise in serum levels of FBG, ALT, AST, TB, TC, TG, and LDL in comparison with the corresponding control group. Co-treatment with AGM (40 & 80 mg/kg) and silymarin significantly alleviated hyperglycemia and amended hepatic biomarkers that was reflected on improved histopathological changes. Conclusion: The current data suggest that oral AGM co-treatment could have a hepatoprotective effect against T2DM associated with NAFLD in rats. Further investigations are recommended to elucidate molecular mechanisms accountable for the useful effects of AGM on hepatocytes.

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 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 Obesity and Insulin Resistance: An Abridged Molecular Correlation

2013 ◽  
Vol 6 ◽  
pp. LPI.S10805 ◽  
Author(s):  
Biswajit Mukherjee ◽  
Chowdhury M. Hossain ◽  
Laboni Mondal ◽  
Paramita Paul ◽  
Miltu K. Ghosh
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Cardiovascular Complications ◽  
Vital Role ◽  
Diabetic Patients ◽  
Predisposing Factor ◽  
Main Culprit

A relationship between obesity and type 2 diabetes is now generally well accepted. This relationship represents several major health hazards including morbid obesity and cardiovascular complications worldwide. Diabetes mellitus is a complex metabolic disorder characterized by impaired insulin release and insulin resistance. Lipids play an important physiological role in skeletal muscle, heart, liver and pancreas. Deregulation of fatty acid metabolism is the main culprit for developing insulin resistance and type 2 diabetes. A predominant predisposing factor to developing obesity, insulin resistance and type 2 diabetes is the permanent elevation of free fatty acids in plasma followed by impaired utilization of lipids by muscle. Diabetes-induced inflammation and oxidative stress have also vital role for development of insulin resistance in diabetic patients. The present review is intended to describe the correlation between lipids, obesity and insulin resistance based on current literature, in order to elucidate involved molecular mechanisms in depth.

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.

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