scholarly journals Changes in protein expression due to metformin treatment and hyperinsulinemia in a human endometrial cancer cell line

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248103
Author(s):  
Carsten Lange ◽  
Amanda Machado Weber ◽  
Ronny Schmidt ◽  
Christoph Schroeder ◽  
Thomas Strowitzki ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Endometrial Cancer ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Patients ◽  
Metformin Treatment ◽  
Type Ii ◽  
Anti Cancer ◽  
Cancer Activity

The incidence of endometrial cancer (EC) has increased over the past years and mainly affects women above the age of 45 years. Metabolic diseases such as obesity and type II diabetes mellitus as well as associated conditions like polycystic ovary syndrome (PCOS), insulin resistance and hyperinsulinemia lead to elevated levels of circulating estrogens. Increased estrogen concentrations, in turn, further trigger the proliferation of endometrial cells and thus promote EC development and progression, especially in the absence of progesterone as seen in postmenopausal women. Elevated blood glucose levels in diabetic patients further contribute to the risk of EC development. Metformin is an insulin-sensitizing biguanide drug, commonly used in the treatment of type II diabetes mellitus, especially in obese patients. Besides its effects on glucose metabolism, metformin displayed anti-cancer effects in various cancer types, including EC. Direct anti-cancer effects of metformin target signaling pathways that are involved in cellular growth and proliferation, e.g. the AKT/PKB/mTOR pathway. Further proteins and pathways have been suggested as potential targets, but the underlying mechanism of action of metformin’s anti-cancer activity is still not completely understood. In the present study, the effects of metformin on protein expression were investigated in the human EC cell line HEC-1A using an affinity proteomic approach. Cells were treated with 0.5 mmol/L metformin over a period of 7 days and changes in the expression pattern of 1,300 different proteins were compared to the expression in untreated control cells as well as insulin-treated cells. Insulin treatment (100 ng/mL) was incorporated into the study in order to implement a model for insulin resistance and associated hyperinsulinemia, conditions that are often observed in obese and diabetic patients. Furthermore, the culture medium was supplemented with 10 nmol/L ß-estradiol (E2) during treatments to mimic increased estrogen levels, a common risk factor for EC development. Based on the most prominent and significant changes in expression, a set of 80 proteins was selected and subjected to a more detailed analysis. The data revealed that metformin and insulin targeted similar pathways in the present study and mostly acted on proteins related to proliferation, migration and tumor immune response. These pathways may be affected in a tumor-promoting as well as a tumor-suppressing way by either metformin treatment or insulin supplementation. The consequences for the cells resulting from the detected expression changes were discussed in detail for several proteins. The presented data helps identify potential targets affected by metformin treatment in EC and allows for a better understanding of the mechanism of action of the biguanide drug’s anti-cancer activity. However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1. Further proteins might be of interest, where metformin counteracted unfavorable effects that have been induced by hyperinsulinemia.

scholarly journals The Severity of Non-Alcoholic Fatty Liver in Type II Diabetes

2018 ◽  
Vol 15 (6) ◽  
pp. 37-42
Author(s):  
Ovidiu Paul Calapod ◽  
Andreea Maria Marin ◽  
Laura Carina Tribus ◽  
Carmen Fierbinţeanu-Braticevici
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Patients ◽  
Type Ii ◽  
Alcoholic Fatty Liver

AbstractNonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects up to one third of the adult population of industrialized countries. The pathophysiological spectrum includes the following entities that are clinically and histologically distinct: hepatic steatosis and steatohepatitis; their subsequent evolution can lead to cirrhosis and hepatocellular carcinoma.The increase of the prevalence of NAFLD during the last decade is caused by the epidemiological and pathophysiological association with type II diabetes and obesity, NAFLD being present in about 70-80% of patients with type II diabetes mellitus. It has long been thought that the relationship between type II diabetes mellitus and NAFLD is unidirectional, fatty liver being secondary to insulin resistance and type II diabetes mellitus, but recent studies show that hepatic steatosis may precede insulin resistance and diabetes mellitus, thus demonstrating abidirectional causal relationship between these two disorders. Weight loss through diet andexercise is effective in preventing and treating NAFLD in diabetic patients; also, drugs that causeweight loss need to be evaluated. Both anti-diabetic medication and statins play an important vrole in the prevention and treatment of NAFLD.

scholarly journals Antioxidant status in type ii diabetes mellitus patients with or without microvascular complications

2007 ◽  
Vol 135 (3-4) ◽  
pp. 143-146 ◽  
Author(s):  
Nada Kostic ◽  
Zorica Caparevic ◽  
Sanja Ilic
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Antioxidant Status ◽  
Ldl Cholesterol ◽  
Type Ii Diabetes Mellitus ◽  
Antioxidant Systems ◽  
Diabetic Patients ◽  
Compensatory Mechanism ◽  
Type Ii ◽  
Pai 1

Introduction. Lipid peroxidation and antioxidant systems are important factors affecting the metabolism of lipoproteins in diabetes mellitus. Objective. The aim of this study was to investigate the lipid and antioxidant parameters in type II diabetes mellitus patients, and also to determine the effect of diabetic complications on these parameters. Method. Lipid status, Oxidized LDL cholesterol, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) levels in plasma of 50 type II diabetic patients were measured with commercially available kits. Results. The results showed only statistically significant higher levels of triglycerides (3.12?3.9 mmol/l) in diabetics compared with the controls. Ox-LDL cholesterol (84.7?16.9 mmol/l) and SOD activities (913.4?120.3 U/gHb) in type 2 diabetes mellitus were higher than those of the controls, but there was no statistical significance. On the other hand, in patients with diabetes mellitus and complications, LDL cholesterol, PAI-1, SOD and GSH-Px activities were higher but not significantly than those without complications. Triglycerides and Ox-LDL cholesterol were lower in the group of diabetic patients with complications in comparison to the group without complications. Conclusion. These results indicate that antioxidant status may be affected in type II diabetic patients and that the rise in some enzyme activities could be a compensatory mechanism to prevent tissue damage. Our results suggest that the rise in PAI-1 in type II diabetics with complications may be a good marker of vascular endothelial dysfunction.

scholarly journals A Study on Serum Uric Acid Level in Type II Diabetes Mellitus

2021 ◽  
Vol 15 (7) ◽  
pp. 2317-2319
Author(s):  
Kashif Ali Samin ◽  
Khalil Ullah ◽  
Muhammad Ikram Shah ◽  
Abidamateen Ansari ◽  
Sadia Khalil ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Type Ii Diabetes ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Patients ◽  
Type Ii

Background and Aim: Morbidity and mortality from non-communicable diseases, particularly diabetes are increasing rapidly in Pakistan, the prevalence has reached 17.1%. A strong association has been witnessed between type II diabetes mellitus with atherosclerosis and serum uric acid level. The current study aim was to assess the levels of serum uric acid in type II diabetes mellitus. Materials and Methods: This cross-sectional study was carried out on 85 diagnosed patients of type II diabetes mellitus in Diabetes hospital, Peshawar and the Department of General Medicine, Shaikh Zayed Medical Complex, Lahore during the period from March 2020 to August 2020.Type II diabetes mellitus (DM) diagnosed patients 85 and healthy control 30 were evaluated in this study. The level of hyperuricemia was defined for women > 6 mg/dl and men >7 mg/dl in men. Results: In this study, a total of 85 diabetic diagnosed patients and 30 healthy controls were enrolled. No significant differences were there in the baseline characteristics like anthropometric and socio-demographic parameters. The mean age for diagnosed and control cases was 58.6±8.7 and 56.5±7.6 years with an age range of 40 and 80 years. Hyperuricemia proportion among diabetic patients was 12.13% while none of the control cases had hyperuricemia. The uric acid means level increased from 4.29±0.81 mg/dl with a diabetic duration between 3 and 4 years to 4.59±0.99 mg/dl with a diabetic duration of 5 to 7 years. Furthermore, mean serum uric acid level reached 6.50±1.08 in cases with diabetic duration 8 to 12 years. Statistically, a significant association was found between diabetic duration and serum uric acid. Also, a positive correlation was found in hyperlipidemia, serum uric acid levels, and hypertension. Conclusion: In diabetic patients serum uric acid levels were found to be significantly higher. Diabetic patients had hypertension, elevated serum uric acid levels, and high triglycerides with dyslipidemia. The rise in serum uric acid levels is proportional to the duration of diabetes. Keywords: Serum uric acid, Type 2 diabetes mellitus, Hypertension

scholarly journals Elevated serum uric acid and triglycerides level in the patients with Type II Diabetes Mellitus- a Nepalese case control study

2017 ◽  
Vol 2 (2) ◽  
pp. 26-34
Author(s):  
Hridaya Parajuli ◽  
Jyotsna Shakya ◽  
Bashu Dev Pardhe ◽  
Puspa Raj Khanal ◽  
Narayan Prasad Parajuli ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Patients ◽  
Type Ii ◽  
Significant Difference

Background: Hyperuricemia is associated with type 2 diabetes, which is a metabolic disorder of multiple etiologies resulting from defects in insulin action. The present study wascarried out to look for any association between uric acid and Type II Diabetes Mellitus and also status of triacylglycerol level among those patients.Methods: The blood samples were collected 100 diabetic and 100 non-diabetic individuals in the department of biochemistry and then analyzed for estimation of blood glucose, Uric Acid and Triacylglycerol level.Results: The average level of serum uric acid in diabetic patients was higher (5.706±1.617) in comparison to non diabetic subjects (4.322±0.784) with statistically significant difference (p≤0.05). For female the result indicate there was a positive correlation between (FBS and triglycerides) and (triglycerides and uric acids) which was statistically significant (r =-0.465, n = 41, p = 0.002) and(r =-0.370, n = 41, p = 0.017) respectively.Conclusions: This study documents that hyperuricemia is associated with type 2 diabetes mellitus. Furthermore, the serum triacylglycerol and serum uric acid is also found to be associated risk factors for diabetic complications. Hence, timely diagnosis and management of diabetes is vital to control the complications related to diabetes.Ann. Clin. Chem. Lab. Med. 2016:2(1); 26-34

scholarly journals Comparison of Inflammatory Markers like C - Reactive Protein, Total Leukocyte Count and Erythrocyte Sedimentation Rate in Type II Diabetes Mellitus

2018 ◽  
Vol 08 (01) ◽  
pp. 11-14
Author(s):  
Aditya Mungamuri ◽  
Sunil Kumar Y. ◽  
Suchetha Kumari N. ◽  
Ullal Harshini Devi
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Inflammatory Markers ◽  
Leukocyte Count ◽  
Type Ii Diabetes Mellitus ◽  
Total Leukocyte Count ◽  
Diabetic Patients ◽  
Type Ii ◽  
Antidiabetic Treatment ◽  
Normal Individuals

Abstract Background: Diabetes Mellitus (DM) has become an epidemic in the 21st century where India leads the world with largest number of patients. There is increasing evidence that inflammation is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidaemia and atherosclerosis. Many previous studies indicate inflammatory markers like CRP, IL-6, IL-8, TNF-alpha, fibrinogen, total sialic acid, ceruloplasmin and total leucocyte count (TLC) are raised in Type II Diabetes Mellitus. However, not many studies have done association of ESR and TLC in DM. Aims: In the present study inflammatory markers like CRP, total leukocyte count and ESR were compared in diabetic and non-diabetic patients. Materials and Methods: 5mL of venous blood was taken from the study subjects.CRP, TLC and ESR was estimated. Results: There was a significant rise in the CRP, TLC and ESR values seen in patients diagnosed with type II diabetes mellitus when compared to normal individuals. All three parameters (CRP, TLC, and ESR) were raised in a total of 7 cases (14%). 14 cases (28%) showed elevated levels of both CRP and ESR. A significant 8 cases (16%) showed elevation of CRP alone. There was a rise of ESR alone in 5 cases (10%). Conclusion: CRP, TLC and ESR are elevated in diabetic patients in comparison to normal individuals. These increase the risk of diabetic related complications like atherosclerosis and dyslipaedemia. Hence, anti-inflammatory drugs in combination with antidiabetic treatment can delay these complications.

To Study the Effect of Type II Diabetes Mellitus and Its Duration on Hearing

2017 ◽  
Vol 2 (3) ◽  
pp. 140-143
Author(s):  
Sameer Aggarwal ◽  
Vikas Kakkar ◽  
Chandni Sharma ◽  
Surender Bishnoi ◽  
Ankit Gulati ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hearing Loss ◽  
Type Ii Diabetes ◽  
Pure Tone Audiometry ◽  
Type Ii Diabetes Mellitus ◽  
Control Group ◽  
Diabetic Patients ◽  
Age Group ◽  
Type Ii ◽  
Group I

ABSTRACT Objective This study has been undertaken to study the effect of type II diabetes mellitus (T2DM) and its duration on hearing. Materials and methods The present study was conducted on 100 persons of age group 20 to 45 years. All subjects included in the study were divided into two groups. Group I: 50 patients suffering from T2DM (fasting blood sugar ≥ 126 mg/dL and postprandial ≥ 200 mg/dL) of either sex, in the age group of 20 to 45 years. Group II: 50 healthy volunteers in the age group of 20 to 45 years, of either sex were included in control group. Hearing assessment was done by using pure tone audiometry (PTA). Results In diabetic patients, the mean threshold in the PTA was higher at all frequencies as compared with healthy controls, and there was a positive correlation between the duration of diabetes and hearing loss. Conclusion Various audiological investigations have revealed that there is a strong association of diabetes with sensorineural part. The prevalence of sensorineural hearing loss (SNHL) in type II diabetics observed was 64%. In the majority of the patients, the hearing loss was bilateral, affecting mid and higher frequencies from 2 to 8 kHz. Hence, to conclude, we can say that the high prevalence of hearing loss in T2DM supports the importance of audiometric evaluation in such patients. How to cite this article Gulati A, Kakkar V, Aggarwal S, Sharma C, Panchal V, Pareek M, Bishnoi S. To Study the Effect of Type II Diabetes Mellitus and Its Duration on Hearing. Int J Adv Integ Med Sci 2017;2(3):140-143.

Study of Prevalence of Hypomagnesemia in Patients with Type II Diabetes Mellitus

2017 ◽  
Vol 3 (2) ◽  
pp. 55-58 ◽  
Author(s):  
NH Rekha ◽  
MS Bharath ◽  
SP Channakeshava
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Negative Impact ◽  
Serum Magnesium ◽  
Fasting Blood Glucose ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Patients ◽  
Type Ii ◽  
Major Health ◽  
Medical College

ABSTRACT Introduction Diabetes mellitus is a common metabolic disorder. Prevalence of diabetes is increasing globally and it is one of the major health problems of the 21st century. The disturbance in serum magnesium (SMg) has been reported among patients with type II diabetes mellitus. Hypomagnesemia has negative impact on glucose homeostasis and insulin sensitivity in patients with type II diabetes mellitus. Aim This study was undertaken to know the prevalence of hypomagnesemia in patients with type II diabetes mellitus and its relation with glycated hemoglobin (HbA1c). The study was conducted on 200 patients with type II diabetes and 100 healthy controls at RajaRajeswari Medical College & Hospital, Bengaluru. Results Out of 200 diabetic patients, 115 (57%) had hypomagnesemia. We observed mean SMg (1.7 mg) significantly low in diabetic patients compared with controls (2.1 mg). We also found HbA1c was high (9%) in hypomagnesemia patients. We found that diabetic hypomagnesemic patients had high mean fasting blood glucose (242.6 mg%) and postprandial blood sugar (313 mg%) than controls. How to cite this article Rekha NH, Bharath MS, Channakeshava SP. Study of Prevalence of Hypomagnesemia in Patients with Type II Diabetes Mellitus. J Med Sci 2017;3(2):55-58.

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