Defects In Insulin Action Research Articles

Dijabetska vaskularna bolest - ćelijski i molekulski pristup

The term diabetes mellitus refers to a state of chronic hyperglycemia due to absolute or relative deficiency of insulin secretion with disordered metabolism of carbohydrates, lipids and proteins. More than 35 million people in Europe are diagnosed with diabetes. In 2030, it is expected that this figure will rise to 43 million. According to the International diabetes federation (IDF), more than 415 million people around the world are diagnosed with diabetes, and in 2040, IDF estimates that 642 million people will have diabetes. The metabolic syndrome (cluster of more or less related metabolic and cardiovascular derangements including visceral obesity, insulin resistance, dyslipidemia, hypertension and glucose intolerance) significantly contributes to development of diabetes mellitus type 2. This syndrome is characterized by a primary cellular defect in insulin action due to disorders in insulin signal transduction (insulin is unable to achieve its biological effects adequately). Under these conditions, insulin resistance in combination with hyperinsulinemia causes numerous metabolic and cardiovascular disorders that are a leading cause of morbidity and mortality worldwide. Thus, 65% of people with diabetes around the world die from cardiovascular disease. Besides, this serious condition is manifested by development of chronic angiopathic complications, such as micro-angiopathy and atherosclerosis. Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Pathogenesis of accelerated atherosclerosis in people with diabetes is not fully understood. Endothelial dysfunction is recognized as the crucial step in atherogenesis. A lot of studies have confirmed the role of dyslipidemia, hyperglycemia, oxidative stress and various mediators of inflammation in initial proatherogenic processes. After foam cell formation, mediators of inflammation initiate a series of intracellular events that include the induction of inflammatory cytokines. Thus, a vicious circle of inflammation, modification of lipoproteins and further inflammation can be maintained in the artery. Inflammatory process, matrix-degrading metalloproteinases activity, platelets aggregation and smooth muscle cells proliferation play a central role in development of fibrotic plaque. It has been shown that inflammation is closely related to the development of atherosclerotic plaque rupture. Having in mind an increase in diabetic vascular disease prevalence in future, it is necessary to take preventive actions to decrease the risk factors (inappropriate diet rich in carbohydrates and saturated fatty acids, smoking, sedentary lifestyle and physical inactivity). Apart from lifestyle changes, the usage of hypocaloric diet and increasing the level of physical activity, in patients with diabetic vascular disease, it is necessary to apply psychoeducation, as well as appropriate cognitive behavioral and medical therapy. However, although various studies related to this health problem have been carried out, scientists are still far from a complete understanding of the cellular and molecular basis of this problem.

Phytochemicals for Non-insulin Diabetes Mellitus: A Minireview on Plant-Derived Compounds Hypoglycemic Activity

Diabetes mellitus (DM), a group of chronic metabolic disorders characterized by hyperglycemia resulting from defects in insulin action and/or insulin secretion. It represents one of the main contributors to ill health and premature mortality worldwide and its prevalence has been rising during the last decades. Unfortunately, many antidiabetic agents for diabetes either have inadequate efficacy or significant mechanism-based side effects. A great deal of interest has been developed to the various natural bioactive compounds isolated and characterized from medicinal plants. This review focuses specifically on four nature phytochemicals such as polysaccharides, flavonoids, saponins and alkaloids whose properties are potencial to antidiabetic remedy.

Diagnostic Approaches to Diabetes Mellitus and the Role of Vitamins

Diabetes mellitus is a group of heterogeneous disorders commonly characterized by chronic hyperglycemia and glucose intolerance, as a result of defects in insulin secretion, defective insulin action, or both. Based on the aetiology and clinical presentation, diabetes mellitus is classified as either immune-mediated (Type 1 diabetes), insulin resistance (Type 2), gestational or others (environment, genetic defects, infections, and certain drugs). The major types of diabetes are type 1 and type 2. Type 1 diabetes is immune mediated and is caused by destruction to the islets cells of the pancreas while type 2 diabetes is caused by a combination of genetic factors related to impaired insulin secretion, insulin resistance and environmental factors such as obesity, overeating, lack of exercise and stress, as well as ageing. The progression of the disease there occurs tissue and vascular damages. This damage ultimately causes severe complications such as retinopathy, neuropathy, nephropathy, cardiovascular complications and ulceration. As diabetes mellitus is associated with severe medical complications it ultimately leads to premature death. The complications of diabetes are due to multiple factors, cellular pathways etc. Oxidative stress is one of the factors that cause this complication by generation of free radicals. The damage caused by these reactive free radicals can be minimized by the antioxidant capacity of vitamins especially vitamin C, E, A and others. Besides these the role played by some minerals is also critical. There are several parameters which can serve as a diagnostic to diabetes. Utilizing the methods for the measurement of these biomarkers is thus very critical and of utmost importance. Some of the diagnostic markers which can be utilized for the type of diabetes a patient is suffering from are blood sugar, HbA1c, c-peptide, GADA, glycated albumin and glycated proteins. The main idea and concern of writing this review is to explores diabetes mellitus in terms of its past historical perspective, biochemical basis, economic burden, management steps along with the future perspectives which needs to be taken to minimize the great loss of damage caused by this metabolic disorder.

Altered levels of serum Copper, Magnesium as a marker of oxidative stress in Predicting Systemic Inflammation in Type 2 Diabetes

Introduction: Diabetes Mellitus is a metabolic disease characterized by hyperglycemia due to defective insulin secretion or action. Trace elements like Copper(Cu) and magnesium (Mg) have been found to be altered in diabetes mellitus and induce reactive oxygen species which has got role in progression of disease. Malondialdehyde (MDA) is a surrogate marker of oxidative stress in type 2 diabetes mellitus. Aims And Objectives: Propose of the study was to estimate serum magnesium (Mg), copper and MDA levels in type 2 diabetes mellitus patients and to compare with that of healthy individuals, also to identify the interrelationship among these and copper &magnesium can be used as an alternate marker of oxidative stress when MDA not available. Materials And Methods:The study included 75 control healthy individuals without Type2 DM and 75 Cases with type 2 DM. Serum concentrations of Glucose, Total Cholesterol, Triglycerides, LDL-C, HDL-C, HbA1c, Magnesium, Copper and MDA was measured. Student's t-test, Pearson correlations tests were used for statistical analysis. Results And Observations: The serum copper level was found to be significantly increased in type 2 DM with HbA1C >7% (157.32±16.89) when compared to control (106.24±25.99). The serum Mg level was found to be significantly decreased (1.62±0.29) (p 7 when compared to control (1.82±0.18). We found a significant increased level of serum Total Cholesterol and LDL-c and Triglycerides and decreased HDL-c in type 2 DM subjects with (p 7% when compared to control. MDA (4.62+1.17nmol/L) in type 2 DM patients when compared to controls(1.4+0.8 nmol/L)( p< 0.0001). Overall, mean serum MDA level in the study group was significantly higher than in the controls. Conclusion: Patients with DM had altered metabolism of Cu (hypercuprimiea) and Mg (hypomagnesaemia). As Cu and Mg has got role in metal induced free radical formation which leads to oxidative stress we compared with novel oxidative marker MDA and concluded that these two trace elements can be used as marker of oxidative stress, which can predict systemic inflammation in type 2 DM to prevent well know complication in advance

Role of miRNAs in the pathogenesis and susceptibility of diabetes mellitus.

MicroRNAs (miRNAs) are noncoding RNAs of ~22 nucleotides that regulate gene expression post-transcriptionally by binding to the 3' untranslated region of messenger RNA (mRNAs), resulting in inhibition of translation or mRNA degradation. miRNAs have a key role in fine-tuning cellular functions such as proliferation, differentiation and apoptosis, and they are involved in carcinogenesis, glucose homeostasis, inflammation and other biological processes. In this review, we focus on the role of miRNAs in the pathophysiology of the metabolic disease and diabetes mellitus, the hallmark of which is hyperglycemia caused by defective insulin secretion and/or action. A growing number of studies have revealed the association between miRNAs and the processes of insulin production and secretion in pancreatic β cells. In addition, aberrant expression of miRNAs in skeletal muscle, adipose tissue and liver has also been reported. Intriguingly, the tumor suppressor p53 has been implicated in the pathogenesis of diabetes in association with a number of miRNAs, suggesting that a p53/miRNA pathway might be a therapeutic target. Moreover, data from genome-wide association studies have revealed that several miRNA target sequences overlap type 2 diabetes susceptibility loci. Finally, the recent discovery of circulating miRNAs associated with diabetes onset/progression suggests the potential use of miRNAs as biomarkers.

Dissecting PUGNAc-mediated inhibition of the pro-survival action of insulin.

Previous studies utilizing PUGNAc, the most widely used β-N-acetylglucosaminidase (OGA) inhibitor to increase global O-N-acetylglucosamine (GlcNAc) levels, have reported a variety of effects including insulin resistance as a direct result of elevated O-GlcNAc levels. The notion of OGA inhibition causing insulin resistance was not replicated in studies in which elevated global O-GlcNAc levels were achieved using two other OGA inhibitors. Related to insulin action, work by others has suggested that O-GlcNAc elevation may inhibit the anti-apoptotic action of insulin. Thus, we examined the pro-survival action of insulin upon serum deprivation in the presence of PUGNAc as well as two selective OGA inhibitors (GlcNAcstatin-g and Thiamet-G), and a selective lysosomal hexosaminidase inhibitor (INJ2). We established that PUGNAc inhibits the pro-survival action of insulin but this effect is not recapitulated by the selective OGA inhibitors suggesting that elevation in O-GlcNAc levels alone is not responsible for PUGNAc's effect on the anti-apoptotic action of insulin. Further, we demonstrate that a selective hexosaminidase A/B (HexA/B) inhibitor does not impact insulin action suggesting that PUGNAc's effect is not due to inhibition of lysosomal hexosaminidase. Finally, we tested a combination of selective OGA and lysosomal hexosaminidase inhibitors but were not able to recapitulate the inhibition of insulin action generated by PUGNAc alone. These results strongly suggest that the defect in insulin action upon PUGNAc treatment does not derive from its inhibition of OGA or HexA/B, and that there is an unknown target of PUGNAc that is the likely culprit in inhibiting the protective effect of insulin from apoptosis.

A study of liver functions in metabolic syndrome and Type 2 diabetes mellitus

Introduction: Diabetes mellitus is a metabolic disease known by chronic hyperglycemia which results from defective insulin action and secretion. Metabolic syndrome consists of a constellation of metabolic abnormalities that confer increased risk of diabetes mellitus. The aim of the present study was to find out if there is any liver function impairment in patients with metabolic syndrome and type 2 diabetes mellitus. Materials and Methods: 50 controls, 50 individuals with metabolic syndrome and 50 individuals with type 2 diabetes mellitus were selected by purposive sampling technique. Serum levels of ALT, AST, ALP, total bilirubin and albumin were estimated in controls and cases. Results: The mean values of serum ALT,AST,ALP, total bilirubin were significantly increased (p<0.001) and serum albumin levels were significantly decreased (p<0.001) in cases compared to controls. Conclusion: Liver functions are impaired in patients with metabolic syndrome and type 2diabetes mellitus when compared to controls.

Multiple benefits of targeting inflammation in the treatment of type 2 diabetes.

The association between the metabolic syndrome and a pathological activation of the innate immune system is now well established. Thus, defective insulin secretion and action are due, at least in part, to islet, liver and fat inflammation in type 2 diabetes. Furthermore, an inflammatory process also seems to be involved in the development of cardiovascular, renal and ophthalmological complications of this disease. Interestingly, several other inflammatory diseases are associated with the metabolic syndrome, such as psoriasis, gout and rheumatic arthritis. The aim of this review is to discuss the clinical progress of anti-inflammatory drugs in the treatment of type 2 diabetes and then speculate on the possible further development of these drugs, with the aim of using the drugs in combination in order to combat the multiple manifestations of inflammatory diseases. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Simone Baltrusch, DOI: 10.1007/s00125-016-3891-x , and Jerry Nadler and colleagues, DOI: 10.1007/s00125-016-3890-y ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x ).

Prevalence and Risk Factors For Diabetes Mellitus and Impaired Fasting Glucose among Adults Aged 15-64 Years in Gilgel Gibe Field Research Center, Southwest Ethiopia, 2013:Through a Who Step Wise Approach

Background: Diabetes mellitus is a common metabolic disorder resulting from defects in insulin action, production, or both. Despite the huge health and economic burden of diabetes mellitus, prevalence and risk factors of diabetes and pre diabetes mellitus are not well documented in Ethiopia generally and in the study area in particular. Therefore, this study was conducted to determine prevalence of diabetes mellitus and impaired fasting glucose and their risk factors among adults 15-64 years old in Gilgel Gibe Field Research Center. Method and materials: The study was based on secondary data collected from late September 2008 to the end of January 2009 in Gilgel Gibe Field Research Center of Jimma University according to WHO-STEP wise approach in a community setting. A total of 4371, 2653 and 1861adults in the age group of 15-64 years were included for step I, II and III respectively. Odds ratio with 95% confidence interval was estimated using multivariable logistic regression to identify independent predictors of diabetes mellitus and impaired fasting glucose. Results: The crude prevalence of diabetes mellitus and impaired fasting glucose among the study participants was 4.4 % [0.6% self-reported (95% CI: 0.30% 0.80%) vs 3.8% newly diagnosed (95% CI: 0.02 – 0.04)] and 9.7% [95% CI: 0.080.11] respectively. The age adjusted prevalence of DM and IFG to the standard world population was 3.7% [95%CI: 0.17-0.45] and 10.1% [95%CI: 0.32-0.67] respectively. Being male [AOR:3.0 (95%CI: 2.80-5.67)], being in the age group of 35-44 [AOR: 4.5 (95%CI: 3.05-10.23)], being current smoker [AOR:1.8 (95%CI:1.68-3.14)] and physically inactive [AOR:2.3 (95%CI:1.27-4.02)] while having central obesity [AOR: 2.5(95%CI:2.40-4.10)] and being in the age group of 55-64 [AOR:2.1(95%CI:1.69-5.23)]were independent predictors of diabetes mellitus and impaired fasting glucose respectively. Conclusion and recommendation: The prevalence of newly diagnosed diabetes mellitus and impaired fasting glucose was higher than the previous reports in Ethiopia and hence health information dissemination on modifiable risk factors such as smoking and regular physical activities as well as screening of high risk groups to reduce the disease burden are needed.

Estimation of plasma glutathione levels in NIDDM patients with and without cardiovascular disease

Diabetes mellitus is a group of metabolic derangements characterised by hyperglycemia resulting from defective insulin secretion or action or both. Persistent hyperglycemia generates reactive oxygen species causing oxidative damage to cells and various biomolecules. In this study the levels of reduced glutathione antioxidant were estimated in NIDDM patients with cardiovascular disease (n=50) by HPLC method and compared to healthy controls (n=50). The results indicated that plasma glutathione levels are significantly decreased showing that antioxidant defence is lowered in diabetic patients with cardiovascular complications. .

Malay

Diabetes mellitus (DM) is a metabolic disease which is characterized by hyperglycemia. There is either disturbance in insulin secretion or defective insulin action or even a combination of both. Usually, there are few confounding factors like genetic, obesity, sedentary life style, atherosclerosis, and even faulty dietary habits which lead or aggravate DM. Usually, the individual does not care and often the complications resulting from hyperglycaemia are fatal. Complications in DM involve the cardiovascular, musculoskeletal, endocrine, renal and neurological systems in the body. Treatment of diabetic complications is not only costly but it is also a burden on the affected families. The present review discusses the challenges faced in DM with special concern on diet and food habits. Knowledge of proper food consumption may also help an individual combat complication in DM and reduce the mortality and morbidity. DOI : http://dx.doi.org/10.17576/JSKM-2015-1301-05

Weight Loss and the Prevention and Treatment of Type 2 Diabetes Using Lifestyle Therapy, Pharmacotherapy, and Bariatric Surgery: Mechanisms of Action.

Weight loss, whether achieved by lifestyle intervention, pharmacotherapy, or bariatric surgery, is highly effective as a primary interventional strategy in both the prevention and treatment of type 2 diabetes. In high-risk patients with prediabetes and/or metabolic syndrome, weight loss effectively prevents progression to type 2 diabetes mellitus (T2DM) and improves cardiovascular risk factors. These benefits are the result of improvements in insulin resistance, which is central to the pathophysiology of cardiometabolic disease. In patients with T2DM, weight loss improves glycemia, while reducing the need for conventional glucose-lowering medicines, by affecting all three processes that produce and sustain the hyperglycemic state, namely via increments in peripheral insulin sensitivity with improvements in insulin signal transduction at the cellular level, more robust insulin secretory responses, and reduced rates of hepatic glucose production. In both nondiabetic and diabetic subjects, hypocaloric feeding (e.g., treatment with very low-calorie diet or bariatric surgery) produces a rapid improvement in insulin sensitivity due to mobilization of fat from the intramyocellular, intrahepatocellular, and intra-abdominal compartments, and via a more long-term mechanism that correlates with the loss of total body fat. In diabetes, by improving glycemia, weight loss also enhances glucose homeostasis by reversing the defects in insulin action and secretion attributable to glucose toxicity. Regardless of the therapeutic approach, weight loss of ∼ 10 % maximally prevents future diabetes in patients with prediabetes or metabolic syndrome. In T2DM, greater degrees of weight loss lead to progressive improvements in glucose homeostasis. Therefore, when accompanied by greater weight loss, the metabolic benefits following bariatric surgery are generally more pronounced than those achieved following lifestyle and medical treatment. In addition, the mechanisms by which bariatric operations improve diabetes may include both weight-dependent and weight-independent mechanisms, and the latter may involve changes in gut hormones, bile acids, or gut microflora.

Low Circulating 25-Hydroxyvitamin D Concentrations Are Associated with Defects in Insulin Action and Insulin Secretion in Persons with Prediabetes ,

Background: Individuals with prediabetes mellitus (PreDM) and low circulating 25-hydroxyvitamin D [25(OH)D] are at increased risk of type 2 diabetes mellitus (T2DM).Objective: We aimed to determine whether low 25(OH)D concentrations are associated with defects in insulin action and insulin secretion in persons with PreDM.Methods: In this cross-sectional study, we stratified 488 nondiabetic subjects as having PreDM or normal fasting glucose (NFG) and a 25(OH)D concentration ≤20 ng/mL (deficient) or >20 ng/mL (sufficient). We determined insulin resistance by steady state plasma glucose (SSPG) concentration and homeostasis model assessment of insulin resistance (HOMA-IR) and insulin secretion by homeostasis model assessment of β-cell function (HOMA-β). We compared insulin resistance and secretion measures in PreDM and NFG groups; 25(OH)D-deficient and 25(OH)D-sufficient groups; and PreDM-deficient, PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups, adjusting for age, sex, race, body mass index, multivitamin use, and season.Results: In the PreDM group, mean SSPG concentration and HOMA-IR were higher and mean HOMA-β was lower than in the NFG group (P < 0.001 for all comparisons). In the 25(OH)D-deficient group, mean SSPG concentration was higher (P < 0.001), but neither mean HOMA-IR nor HOMA-β was significantly different from that in the 25(OH)D-sufficient group. In the PreDM-deficient subgroup, mean (95% CI) SSPG concentration was higher (P < 0.01) than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [192 (177–207) mg/dL vs. 166 (155–177) mg/dL, 148 (138–159) mg/dL, and 136 (127–144) mg/dL, respectively]. Despite greater insulin resistance, mean HOMA-β was not significantly higher in the PreDM-deficient subgroup than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [98 (85–112) vs. 91 (82–101), 123 (112–136), and 115 (106–124), respectively].Conclusion: Subjects with PreDM and low circulating 25(OH)D concentrations are the subgroup of nondiabetic individuals who are the most insulin resistant and have impaired β-cell function, attributes that put them at enhanced risk of T2DM.

Resveratrol Alleviates Lipid‐Induced Insulin Resistance in Lean, But Not Severely Obese, Myotubes

Excessive lipid exposure is associated with various disease states, including severe obesity (BMI &gt; 40 kg/m2), and can lead to insulin resistance. This whole‐body defect in insulin action following chronic lipid exposure is also observed at the cellular level, as myotubes from severely obese humans have a blunted response to insulin. Resveratrol, a natural polyphenolic compound, has been proposed to improve these defects in insulin signaling; however, it is uncertain whether resveratrol can recover the acute and imprinted defects associated with lipid exposure. To examine this, human skeletal muscle cells were isolated from muscle biopsies obtained from lean (BMI = 21.21 ± 0.50 kg/m2) and severely obese (BMI = 53.41±1.61 kg/m2) individuals, and differentiated into myotubes. Myotubes were exposed to palmitate (0.45 mM) for 16 hours to induce insulin resistance in the presence or absence of resveratrol (0.2 μM). Myotubes were then treated with insulin (100 nM) and harvested for examination of insulin signaling. Palmitate suppressed insulin‐induced phosphorylation of AKT (Ser473) by 38% in lean myotubes, which was rescued with resveratrol treatment. Conversely, in comparison to lean controls, resveratrol treatment did not improve insulin action in obese myotubes. These data show that resveratrol treatment can enhance insulin signaling following acute lipid exposure; however, it cannot improve the inherent defects associated with severe obesity.

Primary defects in lipolysis and insulin action in skeletal muscle cells from type 2 diabetic individuals

A decrease in skeletal muscle lipolysis and hormone sensitive-lipase (HSL) expression has been linked to insulin resistance in obesity. The purpose of this study was to identify potential intrinsic defects in lipid turnover and lipolysis in myotubes established from obese and type 2 diabetic subjects. Lipid trafficking and lipolysis were measured by pulse-chase assay with radiolabeled substrates in myotubes from non-obese/non-diabetic (lean), obese/non-diabetic (obese) and obese/diabetic (T2D) subjects. Lipolytic protein content and level of Akt phosphorylation were measured by Western blot. HSL was overexpressed by adenovirus-mediated gene delivery. Myotubes established from obese and T2D subjects had lower lipolysis (−30–40%) when compared to lean, using oleic acid as precursor. Similar observations were also seen for labelled glycerol. Incorporation of oleic acid into diacylglycerol (DAG) and free fatty acid (FFA) level was lower in T2D myotubes, and acetate incorporation into FFA and complex lipids was also lower in obese and/or T2D subjects. Both protein expression of HSL (but not ATGL) and changes in DAG during lipolysis were markedly lower in cells from obese and T2D when compared to lean subjects. Insulin-stimulated glycogen synthesis (−60%) and Akt phosphorylation (−90%) were lower in myotubes from T2D, however, overexpression of HSL in T2D myotubes did not rescue the diabetic phenotype. In conclusion, intrinsic defects in lipolysis and HSL expression co-exist with reduced insulin action in myotubes from obese T2D subjects. Despite reductions in intramyocellular lipolysis and HSL expression, overexpression of HSL did not rescue defects in insulin action in skeletal myotubes from obese T2D subjects.

Effects of Fenugreek Seed Extract and Swimming Endurance Training on Plasma Glucose and Cardiac Antioxidant Enzymes Activity in Streptozotocin-induced Diabetic Rats

ObjectiveDiabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia condition resulting from defective insulin secretion or resistance insulin action, or both. The purpose of this study was to evaluate the effect of 6 weeks swimming training and Trigonella foenum-graecum seed (fenugreek) extract, alone and in combination, on plasma glucose and cardiac antioxidant enzyme activity of streptozotocin-induced diabetic rats. MethodsFifty male Wistar rats were divided into five groups: diabetic control (DC, n = 8); healthy control (HC, n = 11); swimming training (S, n = 11); swimming training + fenugreek seed extract (1.74 g/kg body weight; SF1, n = 11); and swimming training + fenugreek seed extract (0.87 g/kg body weight; SF2, n = 9). Streptozotocin was used for the induction of diabetes. Results were analyzed using one-way analysis of variance followed by Tukey test. ResultsIn comparison with the DC group, all groups exhibited a significant decrease in body weight (p < 0.05), except for the HC group. SF1 and HC groups showed significant decreases in plasma glucose levels compared with the DC group (p < 0.05). S, SF1, SF2, and HC groups showed significant elevations in cardiac antioxidant enzymes activity in comparison with the DC group. ConclusionThe results indicated that the combination of endurance swimming training and fenugreek seed extract can significantly reduce the plasma glucose levels and increase cardiac antioxidant enzymes activity in diabetic rats. Our findings suggest that this combination could be useful for the treatment of hyperglycemia and cardiac oxidative stress induced by diabetes mellitus.

Povezanost insulinske rezistencije i poremećaja kardiovaskularnog sistema

The metabolic syndrome is a cluster of more or less related metabolic and cardiovascular derangements including visceral obesity, insulin resistance , dislipidemia, hypertension and glucose intolerance. This syndrome is characterized by a primary cellular defect in insulin action due to disorders in insulin signal transduction (insulin is unable adequately to achieve its biological effects). Under these conditions, insulin resistance, in combination with hyperinsulinemia causes a numerous metabolic and cardiovascular disorders, that are leading cause of morbidity and mortality worldwide. From pathophysiological point of view, insulin resistance, as well as adipokines and fatty acids released from metabolically active visceral fat tissue, significantly contributes to development of many chronic diseases (diabetes mellitus /diabetes mellitus/ type 2, hypertension, accelerated atherosclerosis and its cardiovascular and cerebrovascular complications, nonalcoholic fatty liver disease, polycystic ovary syndrome and some malignant diseases / breast cancer, etc./). Having in mind increase of metabolic syndrome prevalence in future, it is necessary to take preventive actions to decrease risk factors (inappropriate diet rich in carbohydrates and saturated fat, obesity, smoking, sedentary lifestyle and physical inactivity). Except to lifestyle changes, usage of hypocaloric diet and increase level of physical activity, in patients with metabolic syndrome it is necessary to apply appropriate medical treatment of some components of the syndrome. Although a numerous studies related to this global medical problem are carrying out, scientists are still far from a complete understanding of the molecular basis of this problem.

Medicinal Plants Used in the Management of Diabetes Mellitus 2015.

Diabetes mellitus is one of the common endocrine disorders prevalent in almost all of the countries. This chronic pathology is characterized by hyperglycemia caused by defective insulin action, insulin secretion, or the combination of both. Prolonged persistence of elevated blood glucose level consequently caused a series of complications such as nephropathy, retinopathy, and cardiomyopathy. Currently available synthetic drugs for treating this disease are found to be associated with many adverse effects. The use of plants in medicine is an age-long practice in various parts of the globe for both preventive and curative purposes. Several warnings have been issued over lack of quality control, scientific evidence for the efficacy, and potential adverse effects of herbal remedies including hepatotoxicity, nephrotoxicity, cardiotoxicity, and reproductive toxicity among others. Despite all of these, reliance on herbs as medicine for the management of diabetes mellitus is still much practiced by a large proportion of the world population because they are readily available and affordable with perceived reduced toxicity. Therefore, with the upsurge of interests in medicinal plants, there is a need for thorough scientific investigations of these plants for both efficacy and potential toxicity. In this issue, we present some recent advances in the use of medicinal plants for treating diabetes mellitus. B. Pang et al. (“Innovative Thoughts of Treating Diabetes from the Perspective of Traditional Chinese Medicine”)presented a review article on the contribution of traditional Chinese medicine to the development of alternative and complementary medicine for the treatment and prevention of diabetes mellitus. In another paper (“Effect of Rhizoma Coptidis (Huang Lian) on Treating Diabetes Mellitus”), B. Pang et al. discussed the efficacy and safety of Rhizoma Coptidis in the treatment of diabetes mellitus. In another study (“Evaluation of the Effects of Cornus mas L. Fruit Extract on Glycemic Control and Insulin Level in Type 2 Diabetic Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial”), R. Soltani et al. reported the results of a clinical trial on the effect of Cornus mas L. fruit extract on hyperglycemia in type 2 diabetic patients. In addition, W. Liu et al. (“The Effects of Chinese Medicine on Activation of Wnt/β-Catenin Signal Pathway under High Glucose Condition”) present a valuable review on some compounds implicated in the regulation of Wnt/β-catenin signal pathway as a mechanism of action involved in the antihyperglycemic activity from Chinese medicine. Furthermore, A. O. T. Ashafa and M. I. Kazeem (“Toxicopathological Evaluation of Hydroethanol Extract of Dianthus basuticus in Wistar Rats”) reported on the effects of Dianthus basuticus (a Basotho plant with acclaimed antidiabetic activity) on some biochemical parameters and histology of Wistar rats. Finally, X.-J. Li et al. (“TCM Formula Xiaoyaosan Decoction Improves Depressive-Like Behaviors in Rats with Type 2 Diabetes”) evaluated the effect of traditional medicine formula, Xiaoyaosan, on the cognitive function of diabetic rats. After the first volume of this special issue that was published in 2014, we hope that this issue will present additional valuable information for scientists and clinicians.

Glucose-dependent Foxo1 switch in healing wounds: a shred of hope for diabetic ulcers?

Diabetes mellitus (DM) has been labeled the epidemic of the 21st century, claiming its toll on both quality and duration of life and posing a major economic burden to society (1). By the year 2050, it is predicted that 10% of the population will be diagnosed with DM. Approximately 15% of diabetic patients will develop a nonhealing wound or diabetic foot ulcer. These wounds are the number one cause of lower-limb amputations (2). Several defects have been proposed to explain impaired wound healing in diabetic patients including compromised angiogenesis, inadequate expression of growth factors, excessive cytokine release at the site of injury, reduced epithelial cell migration, and proliferation and defective insulin action in the skin (3–5). However, the specific molecular events leading to impaired wound repair in DM are still unknown. Against this backdrop, it is perhaps not surprising that effective therapeutic strategies to treat these wounds remain limited. The Foxo1 transcription factor is a member of the evolutionarily conserved, mammalian forkhead box O class (Foxo) family that also includes Foxo3, Foxo4, and Foxo6. These transcription factors play a major role in diverse processes including cellular differentiation, proliferation, apoptosis, stress resistance, and glucose metabolism. Foxos are negatively regulated by the insulin-like growth factor 1 (IGF1)/insulin pathway, and they are activated by oxidative stress through Jun N-terminal kinase signaling. Foxo regulation is orchestrated …

P38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients

Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic cultured myotubes, which is in keeping with a retained genetic/epigenetic defect of insulin action. We investigated differences in gene expression during differentiation between diabetic and control muscle cell cultures. Microarray analysis was performed using skeletal muscle cell cultures established from type 2 diabetic patients with a family history of type 2 diabetes and clinical evidence of marked insulin resistance and nondiabetic control subjects with no family history of diabetes. Genes and pathways upregulated with differentiation in the diabetic cultures, compared with controls, were identified using Gene Spring and Gene Set Enrichment Analysis. Gene sets upregulated in diabetic myotubes were associated predominantly with inflammation. p38 MAPK was identified as a key regulator of the expression of these proinflammatory gene sets, and p38 MAPK activation was found to be increased in the diabetic vs. control myotubes. Although inhibition of p38 MAPK activity decreased cytokine gene expression from the cultured diabetic myotubes significantly, it did not improve insulin-stimulated glucose uptake. Increased cytokine expression driven by increased p38 MAPK activation is a key feature of cultured myotubes derived from insulin-resistant type 2 diabetic patients. p38 MAPK inhibition decreased cytokine expression but did not affect the retained defect of impaired insulin action in the diabetic muscle cells.