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1.
Article in English | WPRIM | ID: wpr-898119

ABSTRACT

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

2.
Article in English | WPRIM | ID: wpr-898079

ABSTRACT

This study aimed to determine the impact of dysglycemia on myocardial injury and cardiac dysfunction in acute myocardial infarctions (AMIs). From 2005 to 2016, a total of 1,593 patients with AMIs who underwent percutaneous coronary intervention were enrolled. The patients were classified into five groups according to the admission glucose level: ≤80, 81 to 140, 141 to 200, 201 to 260, and ≥261 mg/dL. The clinical and echocardiographic parameters and 30-day mortality were analyzed. The peak troponin I and white blood cell levels had a positive linear relationship to the admission glucose level. The left ventricular ejection fraction had an inverted U-shape trend, and the E/E' ratio was U-shaped based on euglycemia. The 30-day mortality also increased as the admission glucose increased, and the cut-off value for predicting the mortality was 202.5 mg/dL. Dysglycemia, especially hyperglycemia, appears to be associated with myocardial injury and could be another adjunctive parameter for predicting mortality in patients with AMIs.

3.
Article in English | WPRIM | ID: wpr-890415

ABSTRACT

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

4.
Article in English | WPRIM | ID: wpr-890375

ABSTRACT

This study aimed to determine the impact of dysglycemia on myocardial injury and cardiac dysfunction in acute myocardial infarctions (AMIs). From 2005 to 2016, a total of 1,593 patients with AMIs who underwent percutaneous coronary intervention were enrolled. The patients were classified into five groups according to the admission glucose level: ≤80, 81 to 140, 141 to 200, 201 to 260, and ≥261 mg/dL. The clinical and echocardiographic parameters and 30-day mortality were analyzed. The peak troponin I and white blood cell levels had a positive linear relationship to the admission glucose level. The left ventricular ejection fraction had an inverted U-shape trend, and the E/E' ratio was U-shaped based on euglycemia. The 30-day mortality also increased as the admission glucose increased, and the cut-off value for predicting the mortality was 202.5 mg/dL. Dysglycemia, especially hyperglycemia, appears to be associated with myocardial injury and could be another adjunctive parameter for predicting mortality in patients with AMIs.

5.
Article in English | WPRIM | ID: wpr-811145

ABSTRACT

BACKGROUND: Diabetes mellitus (DM) is the most common chronic metabolic disorder with an increasing prevalence worldwide. According to a previous study, physicians' treatment patterns or patients' behaviors change when they become aware of the risk for cardiovascular (CV) disease in patients with DM. However, there exist controversial reports from previous studies in the impact of physicians' behaviors on the patients' quality of life (QoL) improvements. So we investigate the changes in QoL according to physicians and patients' behavioral changes after the awareness of CV risks in patients with type 2 DM.METHODS: Data were obtained from a prospective, observational study where 799 patients aged ≥40 years with type 2 DM were recruited at 24 tertiary hospitals in Korea. Changes in physicians' behaviors were defined as changes in the dose/type of antihypertensive, lipid-lowering, and anti-platelet therapies within 6-month after the awareness of CV risks in patients. Changes in patients' behaviors were based on lifestyle modifications. Audit of Diabetes Dependent Quality of Life comprising 19-life-domains was used.RESULTS: The weighted impact score change for local or long-distance journey (P=0.0049), holidays (P=0.0364), and physical health (P=0.0451) domains significantly differed between the two groups; patients whose physician's behaviors changed showed greater improvement than those whose physician's behaviors did not change.CONCLUSION: This study demonstrates that changes in physicians' behaviors, as a result of perceiving CV risks, improve QoL in some domains of life in DM patients. Physicians should recognize the importance of understanding CV risks and implement appropriate management.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Holidays , Humans , Korea , Life Style , Observational Study , Prevalence , Prospective Studies , Quality of Life , Risk Management , Tertiary Care Centers
6.
Article | WPRIM | ID: wpr-835404

ABSTRACT

Background@#A diabetic foot is the most common cause of non-traumatic lower extremity amputations (LEA). The study seeks to assess the risk factors of amputation in patients with diabetic foot ulcers (DFU). @*Methods@#The study was conducted on 351 patients with DFUs from January 2010 to December 2018. Their demographic characteristics, disease history, laboratory data, ankle-brachial index, Wagner classification, osteomyelitis, sarcopenia index, and ulcer sizes were considered as variables to predict outcome. A chi-square test and multivariate logistic regression analysis were performed to test the relationship of the data gathered. Additionally, the subjects were divided into two groups based on their amputation surgery. @*Results@#Out of the 351 subjects, 170 required LEA. The mean age of the subjects was 61 years and the mean duration of diabetes was 15 years; there was no significant difference between the two groups in terms of these averages. Osteomyelitis (hazard ratio [HR], 6.164; 95% confidence interval [CI], 3.561−10.671), lesion on percutaneous transluminal angioplasty (HR, 2.494; 95% CI, 1.087−5.721), estimated glomerular filtration rate (eGFR; HR, 0.99; 95% CI, 0.981−0.999), ulcer size (HR, 1.247; 95% CI, 1.107−1.405), and forefoot ulcer location (HR, 2.475; 95% CI, 0.224−0.73) were associated with risk of amputation. @*Conclusion@#Osteomyelitis, peripheral artery disease, chronic kidney disease, ulcer size, and forefoot ulcer location were risk factors for amputation in diabetic foot patients. Further investigation would contribute to the establishment of a diabetic foot risk stratification system for Koreans, allowing for optimal individualized treatment.

7.
Article | WPRIM | ID: wpr-832359

ABSTRACT

Background@#To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. @*Methods@#This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. @*Results@#After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771;p <0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; p =0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; p=0.045). @*Conclusion@#The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.

8.
Article | WPRIM | ID: wpr-832341

ABSTRACT

Background@#Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). @*Methods@#From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. @*Results@#In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. @*Conclusion@#This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

9.
Article | WPRIM | ID: wpr-832322

ABSTRACT

Impaired β-cell function is the key pathophysiology of type 2 diabetes mellitus, and chronic exposure of nutrient excess could lead to this tragedy. For preserving β-cell function, it is essential to understand the cause and mechanisms about the progression of β-cells failure. Glucotoxicity, lipotoxicity, and glucolipotoxicity have been suggested to be a major cause of β-cell dysfunction for decades, but not yet fully understood. Fatty acid translocase cluster determinant 36 (CD36), which is part of the free fatty acid (FFA) transporter system, has been identified in several tissues such as muscle, liver, and insulin-producing cells. Several studies have reported that induction of CD36 increases uptake of FFA in several cells, suggesting the functional interplay between glucose and FFA in terms of insulin secretion and oxidative metabolism. However, we do not currently know the regulating mechanism and physiological role of CD36 on glucolipotoxicity in pancreatic β-cells. Also, the downstream and upstream targets of CD36 related signaling have not been defined. In the present review, we will focus on the expression and function of CD36 related signaling in the pancreatic β-cells in response to hyperglycemia and hyperlipidemia (ceramide) along with the clinical studies on the association between CD36 and metabolic disorders.

10.
Article in English | WPRIM | ID: wpr-763662

ABSTRACT

BACKGROUND: The objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older. METHODS: This study used 2013 to 2016 data from the Korea National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%. RESULTS: In 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c <6.5%, blood pressure <140/85 mm Hg, and low density lipoprotein cholesterol <100 mg/dL. Only 8.4% of people with diabetes had good control of all three targets. CONCLUSION: This study confirms that diabetes is as an important public health problem. Efforts should be made to increase awareness, detection, and comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.


Subject(s)
Adult , Blood Pressure , Cholesterol, LDL , Comorbidity , Diabetes Mellitus , Fasting , Glucose , Glycated Hemoglobin A , Humans , Hypercholesterolemia , Hypertension , Korea , Mortality , Nutrition Surveys , Obesity , Obesity, Abdominal , Prevalence , Public Health , Republic of Korea
11.
Article in English | WPRIM | ID: wpr-739802

ABSTRACT

BACKGROUND: Chronic hyperglycemia has deleterious effects on pancreatic β-cell function and turnover. Recent studies support the view that cyclin-dependent kinase 5 (CDK5) plays a role in β-cell failure under hyperglycemic conditions. However, little is known about how CDK5 impair β-cell function. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. In this study, we examined the effect of myricetin on high glucose (HG)-induced β-cell apoptosis and explored the relationship between myricetin and CDK5. METHODS: To address this question, we subjected INS-1 cells and isolated rat islets to HG conditions (30 mM) in the presence or absence of myricetin. Docking studies were conducted to validate the interaction between myricetin and CDK5. Gene expression and protein levels of endoplasmic reticulum (ER) stress markers were measured by real-time reverse transcription polymerase chain reaction and Western blot analysis. RESULTS: Activation of CDK5 in response to HG coupled with the induction of ER stress via the down regulation of sarcoendoplasmic reticulum calcium ATPase 2b (SERCA2b) gene expression and reduced the nuclear accumulation of pancreatic duodenal homeobox 1 (PDX1) leads to β-cell apoptosis. Docking study predicts that myricetin inhibit CDK5 activation by direct binding in the ATP-binding pocket. Myricetin counteracted the decrease in the levels of PDX1 and SERCA2b by HG. Moreover, myricetin attenuated HG-induced apoptosis in INS-1 cells and rat islets and reduce the mitochondrial dysfunction by decreasing reactive oxygen species production and mitochondrial membrane potential (Δψm) loss. CONCLUSION: Myricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.


Subject(s)
Animals , Apoptosis , Blotting, Western , Calcium-Transporting ATPases , Cyclin-Dependent Kinase 5 , Diabetes Mellitus, Type 2 , Down-Regulation , Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Gene Expression , Genes, Homeobox , Glucose , Hyperglycemia , Insulin-Secreting Cells , Membrane Potential, Mitochondrial , Polymerase Chain Reaction , Rats , Reactive Oxygen Species , Reticulum , Reverse Transcription , Up-Regulation
12.
Article in English | WPRIM | ID: wpr-717360

ABSTRACT

BACKGROUND: This report presents the recent prevalence and comorbidities related to diabetes in Korea by analyzing the nationally representative data. METHODS: Using data from the Korea National Health and Nutrition Examination Survey for 2013 to 2014, the percentages and the total number of subjects over the age of 30 years with diabetes and prediabetes were estimated and applied to the National Population Census in 2014. Diagnosis of diabetes was based on fasting plasma glucose (≥126 mg/dL), current taking of antidiabetic medication, history of previous diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%. Impaired fasting glucose (IFG) was defined by fasting plasma glucose in the range of 100 to 125 mg/dL among those without diabetes. RESULTS: About 4.8 million (13.7%) Korean adults (≥30 years old) had diabetes, and about 8.3 million (24.8%) Korean adults had IFG. However, 29.3% of the subjects with diabetes are not aware of their condition. Of the subjects with diabetes, 48.6% and 54.7% were obese and hypertensive, respectively, and 31.6% had hypercholesterolemia. Although most subjects with diabetes (89.1%) were under medical treatment, and mostly being treated with oral hypoglycemic agents (80.2%), 10.8% have remained untreated. With respect to overall glycemic control, 43.5% reached the target of HbA1c < 7%, whereas 23.3% reached the target when the standard was set to HbA1c < 6.5%, according to the Korean Diabetes Association guideline. CONCLUSION: Diabetes is a major public health threat in Korea, but a significant proportion of adults were not controlling their illness. We need comprehensive approaches to overcome the upcoming diabetes-related disease burden in Korea.


Subject(s)
Adult , Blood Glucose , Censuses , Comorbidity , Diabetes Mellitus , Diagnosis , Fasting , Glucose , Glycated Hemoglobin A , Humans , Hypercholesterolemia , Hypoglycemic Agents , Korea , Nutrition Surveys , Prediabetic State , Prevalence , Public Health , Republic of Korea
13.
Article in English | WPRIM | ID: wpr-716316

ABSTRACT

BACKGROUND: This study aims to describe the trends in the severity and treatment modality of patients with diabetic foot ulcer (DFU) at a single tertiary referral center in Korea over the last 10 years and compare the outcomes before and after the introduction of a multidisciplinary diabetic foot team. METHODS: In this retrospective observational study, electronic medical records of patients from years 2002 to 2015 at single tertiary referral center were reviewed. Based on the year of first admission, patients were assigned to a group either before or after the year 2012, the year the diabetes team launched. RESULTS: Of the 338 patients with DFU, 229 were first admitted until the year 2011 (group A), while 109 were first admitted since the year 2012 (group B). Mean age was higher in group B, and ulcer size was larger than those of group A. Whereas duration of diabetes was longer in group B, glycemic control was improved (mean glycosylated hemoglobin, 9.48% vs. 8.50%). The proportion of minor lower extremity amputation (LEA) was increased, but length of hospital stay was decreased (73.7±79.6 days vs. 39.8±36.9 days). As critical ischemic limb increased, the proportion of major LEA was not decreased. CONCLUSION: Improved glycemic control, multidisciplinary strategies with prompt surgical treatment resulted in reduced length of hospital stay, but these measures did not reduce major LEAs. The increase in critical ischemic limb may have played a role in the unexpected outcome, and may suggest the need for increased vascular intervention strategies in DFU treatment.


Subject(s)
Amputation , Diabetic Foot , Diagnosis , Electronic Health Records , Extremities , Glycated Hemoglobin A , Humans , Korea , Length of Stay , Lower Extremity , Observational Study , Patient Care Team , Retrospective Studies , Tertiary Care Centers , Ulcer
15.
Article in English | WPRIM | ID: wpr-714102

ABSTRACT

BACKGROUND: Hemorheologic indices are known to be related to vascular complications in variable clinical settings. However, little is known about the associations between hemorheologic parameters and acute myocardial infarction (AMI) in type 2 diabetes mellitus (T2DM). The purpose of this study was to demonstrate the changes of hemorheologic environment inside of blood using hemorheologic parameters, especially the elongation index (EI) and critical shear stress (CSS) in diabetics with versus without AMI. METHODS: A total of 195 patients with T2DM were enrolled. Patients were divided into the study group with AMI (AMI+, n = 77) and control group (AMI−, n = 118) who had no history of coronary artery disease. Hemorheologic parameters such as EI and CSS were measured and compared between the two groups. RESULTS: The EI was lower (30.44%±1.77% in AMI+ and 31.47%±1.48% in AMI−, P < 0.001) but the level of CSS was higher (316.13±108.20 mPa in AMI+ and 286.80±85.34 mPa in AMI−, P = 0.040) in the AMI+. The CSS was significantly related to the erythrocyte sedimentation rate (R² = 0.497, P < 0.001) and use of dipeptidyl peptidase-4 inhibitors (R² = 0.574, P = 0.048). CONCLUSION: Diabetics with AMI resulted in adverse hemorheologic changes with lower EI and higher CSS compared to diabetic subjects without AMI. Evaluation of the hemorheologic parameters may provide valuable supplementary information for managing patients with AMI and T2DM.


Subject(s)
Blood Sedimentation , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Erythrocyte Deformability , Hemorheology , Humans , Myocardial Infarction
16.
Article in English | WPRIM | ID: wpr-217839

ABSTRACT

No abstract available.


Subject(s)
Hypertension , Oxidative Stress
17.
Article in English | WPRIM | ID: wpr-29654

ABSTRACT

BACKGROUND: Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance. METHODS: This was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was ‘ln [FPG (mg/dL)×triglyceride (mg/dL)/2],’ and the sCD36 index was ‘ln [sCD36 (pg/mL)×FPG (mg/dL)/2].’ RESULTS: One hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; P<0.05) and negatively with homeostasis model assessment estimate of β-cell function (r=−0.317). The odds ratio (OR) of sCD36 index for T2DM was 4.39 (95% confidential interval, 1.51 to 12.77) after adjusting age, gender, blood pressure, smoking, alcohol, non-high density lipoprotein cholesterol and high-sensitivity C-reactive protein. However, OR of TyG index did not remained significance after adjustment. CONCLUSION: sCD36 index has an independent association with the risk of T2DM, and showed better correlation than TyG index. These results suggest sCD36 index might be useful surrogate marker for the risk of diabetes.


Subject(s)
Atherosclerosis , Biomarkers , Blood Glucose , Blood Pressure , C-Reactive Protein , Cholesterol , Cross-Sectional Studies , Diabetes Mellitus, Type 2 , Fasting , Glucose , Glycated Hemoglobin A , Homeostasis , Humans , Insulin Resistance , Lipoproteins , Odds Ratio , Plasma , Prediabetic State , Prevalence , Smoke , Smoking
18.
Article in English | WPRIM | ID: wpr-174152

ABSTRACT

The incidence of type 2 diabetes mellitus and insulin resistance is growing rapidly. Multiple organs including the liver, skeletal muscle and adipose tissue control insulin sensitivity coordinately, but the mechanism of skeletal muscle insulin resistance has not yet been fully elucidated. However, there is a growing body of evidence that lipotoxicity induced by mitochondrial dysfunction in skeletal muscle is an important mediator of insulin resistance. However, some recent findings suggest that skeletal mitochondrial dysfunction generated by genetic manipulation is not always correlated with insulin resistance in animal models. A high fat diet can provoke insulin resistance despite a coordinate increase in skeletal muscle mitochondria, which implies that mitochondrial dysfunction is not mandatory in insulin resistance. Furthermore, incomplete fatty acid oxidation by excessive nutrition supply compared to mitochondrial demand can induce insulin resistance without preceding impairment of mitochondrial function. Taken together we suggested that skeletal muscle mitochondrial overloading, not mitochondrial dysfunction, plays a pivotal role in insulin resistance.


Subject(s)
Adipose Tissue , Diabetes Mellitus, Type 2 , Diet, High-Fat , Incidence , Insulin Resistance , Insulin , Liver , Mitochondria , Models, Animal , Muscle, Skeletal , Reactive Oxygen Species
19.
Article in English | WPRIM | ID: wpr-787053

ABSTRACT

The incidence of type 2 diabetes mellitus and insulin resistance is growing rapidly. Multiple organs including the liver, skeletal muscle and adipose tissue control insulin sensitivity coordinately, but the mechanism of skeletal muscle insulin resistance has not yet been fully elucidated. However, there is a growing body of evidence that lipotoxicity induced by mitochondrial dysfunction in skeletal muscle is an important mediator of insulin resistance. However, some recent findings suggest that skeletal mitochondrial dysfunction generated by genetic manipulation is not always correlated with insulin resistance in animal models. A high fat diet can provoke insulin resistance despite a coordinate increase in skeletal muscle mitochondria, which implies that mitochondrial dysfunction is not mandatory in insulin resistance. Furthermore, incomplete fatty acid oxidation by excessive nutrition supply compared to mitochondrial demand can induce insulin resistance without preceding impairment of mitochondrial function. Taken together we suggested that skeletal muscle mitochondrial overloading, not mitochondrial dysfunction, plays a pivotal role in insulin resistance.


Subject(s)
Adipose Tissue , Diabetes Mellitus, Type 2 , Diet, High-Fat , Incidence , Insulin Resistance , Insulin , Liver , Mitochondria , Models, Animal , Muscle, Skeletal , Reactive Oxygen Species
20.
Article in English | WPRIM | ID: wpr-58428

ABSTRACT

Inhibition of CD36, a fatty acid transporter, has been reported to prevent glucotoxicity and ameliorate high glucose induced beta cell dysfunction. Ezetimibe is a selective cholesterol absorption inhibitor that blocks Niemann Pick C1-like 1 protein, but may exert its effect through suppression of CD36. We attempted to clarify the beneficial effect of ezetimibe on insulin secreting cells and to determine whether this effect is related to change of CD36 expression. mRNA expression of insulin and CD36, intracellular peroxide level and glucose stimulated insulin secretion (GSIS) under normal (5.6 mM) or high glucose (30 mM) condition in INS-1 cells and primary rat islet cells were compared. Changes of the aforementioned factors with treatment with ezetimibe (20 μM) under normal or high glucose condition were also assessed. mRNA expression of insulin was decreased with high glucose, which was reversed by ezetimibe in both INS-1 cells and primary rat islets. CD36 mRNA expression was increased with high glucose, but decreased by ezetimibe in INS-1 cells and primary rat islets. Three-day treatment with high glucose resulted in an increase in intracellular peroxide level; however, it was decreased by treatment with ezetimibe. Decrease in GSIS by three-day treatment with high glucose was reversed by ezetimibe. Palmitate uptake following exposure to high glucose conditions for three days was significantly elevated, which was reversed by ezetimibe in INS-1 cells. Ezetimibe may prevent glucotoxicity in pancreatic β-cells through a decrease in fatty acid influx via inhibition of CD36.


Subject(s)
Animals , Anticholesteremic Agents/pharmacology , CD36 Antigens/antagonists & inhibitors , Cells, Cultured , Ezetimibe/pharmacology , Flow Cytometry , Glucose/toxicity , Insulin/genetics , Insulin-Secreting Cells/cytology , Male , Palmitic Acid/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction
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