Disorders Of Insulin Secretion Research Articles

Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization.

Childhood obesity is increasing worldwide and presents as a global health issue due to multiple metabolic comorbidities. About 1% of adolescents with obesity develop type 2 diabetes (T2D); however, little is known about the genetic and pathophysiological background at young age. The objective of this study was to assess the prevalence of impaired glucose regulation (IGR) in a large cohort of children and adolescents with obesity and to characterize insulin sensitivity and insulin secretion. We also wanted to investigate adolescents with insulin secretion disorder more closely and analyze possible candidate genes of diabetes in a subcohort. We included children and adolescents with obesity who completed an oral glucose tolerance test (OGTT, glucose + insulin) in the outpatient clinic. We calculated Matsuda index, the area under the curve (AUC (Ins/Glu)), and an oral disposition index (ISSI-2) to estimate insulin resistance and beta-cell function. We identified patients with IGR and low insulin secretion (maximum insulin during OGTT < 200 mU/l) and tested a subgroup using next generation sequencing to identify possible mutations in 103 candidate genes. The total group consisted of 903 children and adolescents with obesity. 4.5% showed impaired fasting glucose, 9.4% impaired glucose tolerance, and 1.2% T2D. Matsuda index and Total AUC (Ins/Glu) showed a hyperbolic relationship. Out of 39 patients with low insulin secretion, we performed genetic testing on 12 patients. We found five monogenetic defects (ABCC8 (n = 3), GCK (n = 1), and GLI2/PTF1A (n = 1)). Using surrogate parameters of beta-cell function and insulin resistance can help identify patients with insulin secretion disorder. A prevalence of 40% mutations of known diabetes genes in the subgroup with low insulin secretion suggests that at least 1.7% of patients with adolescent obesity have monogenic diabetes. A successful molecular genetic diagnosis can help to improve individual therapy.

Caffeic Acid Dimethyl Ether Ameliorates Excessive Glucose and Lipid-Induced Insulin Secretion Dysfunction in Pancreatic Beta-Cells through the miR-378b–PI3K–AKT Pathway

An important factor in the progression of type 2 diabetes mellitus is the malfunctioning insulin production by β-cells in the pancreas. Caffeic acid dimethyl ether (CADE) reduces resistance to insulin in alcoholic fatty liver disease, but both the therapeutic effects of CADE on excessive glucose and lipid-induced insulin secretion disorders and the underlying mechanisms are unknown. The aim of this research was to (i) explore how CADE impacts insulin production issues caused by a surplus of glucose and lipids β-cells and (ii) elucidate the underlying mechanism. The results of our research demonstrated that insulin production was reduced in the pancreas of mice given a high-fat -diet and streptozotocin, as well as in human 1.1B4 pancreatic β-cells treated with high -glucose and high -fat, with increased activity of miR-378b and decreased expression levels of p110α, p-AKT1/2, insulin receptor, p-FoxO1, and PDX-1. However, treatment with CADE ameliorated the insulin secretion impairment by decreasing the miR-378b level and reversing the inhibitory effects on the aforementioned factors. Overexpression of miR-378b exacerbated the insulin secretion disorder and inhibited the PI3K-AKT signaling pathway, whereas miR-378b deficiency relieved the insulin secretion disorder, activating the PI3K-AKT pathway. In addition, CADE ameliorated the impairment of insulin secretion and reversed the miR-378b overexpression-induced PI3K-AKT pathway inhibition. In conclusion, our study demonstrates that CADE ameliorated insulin secretion dysfunction induced by excess lipid and glucose in β-cells by downregulating miR-378b expression, thus promoting PI3K-AKT activation.

Advances in polysaccharides of natural source of anti-diabetes effect and mechanism.

Diabetes is a chronic disease in metabolic disorder, and the pathology is characterized by insulin resistance and insulin secretion disorder in blood. In current, many studies have revealed that polysaccharides extracted from natural sources with significant anti-diabetic effects. Natural polysaccharides can ameliorate diabetes through different action mechanisms. All these polysaccharides are expected to have an important role in the clinic. Existing polysaccharides for the treatment of diabetes are reviewed, and the mechanism of polysaccharides in the treatment of diabetes and its structural characteristics are described in detail. This article introduced the natural polysaccharide through different mechanisms of action in the treatment of diabetes, including oxidative stress, apoptosis, inflammatory response and regulation of intestinal bacteria. Natural polysaccharides can treat of diabetes by regulating signaling pathways is also a research hotspot. In addition, the structural characteristics of polysaccharides were explored. There are some structure-activity relationships between natural polysaccharides and the treatment of diabetes.

Comparison between Serum Vaspin in Chronic Kidney Disease and with Hepatitis C Virus and Normal Control Group

Abstract Background Chronic kidney disease ―CKD|| patients have insulin secretion disorders and resistance to insulin effects, that is responsible for the development of cardiovascular proceedings. Vaspin is an adipcytokine that regulates glucose and lipid metabolism. Aim and objectives To compare serum level of Vaspin in Chronic kidney disease&amp; chronic hepatitis C patients group and normal control group. Subjects and Methods This study is comparative case - control study, was conducted at in Ain shams university hospitals &amp; El Zaitoun Specialized hospital on patients attending gastroenterology and hepatology clinic and nephrology clinic0. Result There was high statistically significant difference between the studied groups as regard vaspin. Conclusion Diabetic nephropathy‖ patients presented a significant increased levels of serum Vaspin when compared to levels to control, serum Vaspin are protective roles. Also, vaspin could be used as specific predictors for liver fibrosis in CHC patients with and without diabetes.

EXPLORING THE ANCIENT WISDOM, SIDDHA INSIGHTS IN MADHUMEGA AVATHAIGAL ILLUSTRATING WITH CHRONIC COMPLICATION OF NON-INSULIN DEPENDENT DIABETES MELLITUS - A LITERATURE REVIEW

Diabetes has spread throughout the world in recent years, and this disease has led to an increase in national and international healthcare costs. There are many causes of this terrible disease, but according to the Siddha system of medicine, the real triggers are the three bodily humors that are the main components of the living body. The term diabetes mellitus is characterized by chronic hyperglycemia of the metabolism of carbohydrates, lipids, and proteins due to metabolic disorders of various etiologies, disorders of insulin secretion, insulin action, or both. Diabetes is a condition comparable to Madhumegam in Siddha. Other names mentioned in the text are Neerizivu and Inippuneer. Common signs and symptoms include increased frequency and volume of urination, pus around the urethra, nausea, and dry skin. This disease is defined as the main disease. Madhumegaavataigal's text from the Siddha School continues to be the primary research authority on diabetes and its complications. Here, ancient and traditional knowledge of the disease is explored with a comparative review of complications of diabetes and MadumeghaAvathaigal in modern classics.

Effect of Purslane (Portulaca oleracea L.) Ethanol Extract in Alloxan-induced Hyperglycemic Rats (Rattus novergicus L.) Blood Glucose Levels

Diabetes mellitus (DM) is a chronic condition which caused by insulin secretion disorder, insulin resistance or both. High number of diabetics per year has led many researchers to conduct research to find the most safe and effective medicine for DM treatment. Flavonoid are known to act as inhibitors of α-amylase as a parameter of pancreatic damage and help lower blood glucose levels. One source of flavonoids is purslane. The aim of this study was to examine the effect of purslane ethanol extract on glucose and α-amylase levels in rat. Twenty rats Rattus novergicus L. strain Wistar are divided into 5 groups; control, positive control, and three test groups, each was given purslane ethanol extract of 100 mg/kgBW, 200 mg/kgBW, and 300 mg/kgBW. Blood glucose and body weight were measured before alloxan induction, after induction, as well as day- 7, 14, 21, and 28; while feed and drink consumption were measured everyday starting with the administration of purslane ethanol extract. The α-amylase test was carried out on the 28th day using enzymatic UV determination of degradation product of maltose and glucose method. The analysis result showed that rats blood glucose and α-amylase decreased in each group with purslane extract. The antioxidant content of flavonoids in purslane ethanol extract has been shown to have anti-diabetic effects by repairing pancreatic function.

Homeostatic microbiome disruption as a cause of insulin secretion disorders. Candida albicans, a new factor in pathogenesis of diabetes: A STROBE compliant cross-sectional study.

The study aimed to test the hypothesis that homeostatic microbiome (HM) disorders lead to the increased indirect influence of certain microorganisms (MO) in the gastrointestinal tract, causing a disorder of insulin secretion, insulin resistance, and diabetes. We highlighted Candida and certain types of bacteria since previous in vitro research showed they significantly affect insulin secretion and can cause insulin resistance in obese patients with metabolic syndrome. After determining the type of MO present in the throat swab and the stool, the oral glucose tolerance test (OGTT) test, and analysis of glucose and insulin secretion were performed in patients (n = 38) who were positive for certain types of MO compared to negative patients. Finally, all patients were divided into two groups: overweight patients (body mass index [BMI] < 30) and obese patients (BMI > 30). These two groups were compared for the percentage of certain types of MO to determine which MO can affect an increase in obesity and BMI. The presence of Diphtheroids in the throat (60.5%) reduces insulin secretion in patients compared with the negative group (194.5: 332.4) and the difference was statistically significant (P = .030). The presence of Candida in the throat (10%) increases insulin secretion, but the difference was statistically insignificant. The presence of Candida in the stool (28.9%) also increases insulin secretion and the difference was statistically significant (P = .038). Cumulative results (throat + stool) were similar (180: 332, P = .022). Analysis of BMI showed that the percentage of Diphtheroids in the throat decreases with increased body weight (53.8: 75%) while the percentage of Candida (38.5: 8.3%) and Enterobacter (61.5: 25%) increases, but these differences were statistically insignificant (P > .05). Diphtheroids in the throat can reduce insulin secretion by synthesizing their metabolites. Candida albicans is a conditional pathogen and as a significant indirect factor induces increased insulin secretion and insulin resistance. There are indications that elevated levels of Candida in the intestinal system can cause increased body weight of patients. C albicans should be considered a new factor in the pathogenesis of diabetes.

Pengaruh Range of Motion (ROM) Aktif Kaki terhadap Sensitivitas Kaki pada Pasien Diabetes Millitus Tipe II di Wilayah Kerja Puskesmas Masbagik

In the era of globalization there is a shift from infectious diseases to non-communicable diseases, more and more degenerative diseases, one of which is Diabetes Millitus. DM is a metabolic disease characterized by increased blood sugar levels due to insulin secretion disorders. Hyperglycemia and metabolic disorders in DM can cause complications, one of which often occurs in DM patient is nerve damage or peripheral neuropathy so that it can cause a decrease in foot sensitivity. The purpose of this study was to determine the influence of foot active range of motion (ROM) on the sensitivity of foot in patients Diabetes Millitus type II in the working area of primary health care Masbagik year 2021. This study is a pre-exsperimental research design with One Grup Pretest-Posttest. Approach. The sample in this study is patients with Diabetes Millitus type II in the working area of primary health care Masbagik 22 people sampel. Sampling technique using Purposive sampling. Statistical test results show that there is an effect of active foot Range Of Motion (ROM) on foot sensitivity in patients Diabetes Millitus type II with P test results, namely p value = 0.000 &lt; a = 0.05, where the null hypothesis (H0) is rejected or the alternative hypothesis (Ha) accepted, It can be concluded that there is an effect of foot active range of motion (ROM) on the sensitivity of foot in patients Diabetes Millitus type II. Respondents are advised to always do Range Of Motion (ROM) active foot of the foot to maintain foot sensitivity. If foot sensitivity is not maintained, the roots experience impaired foot sensitivity which can cause diabetic ulcers or diabetic foot.

Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin.

Background Osteocalcin (OCN) has been proved to be closely related with the development of type 2 diabetes mellitus (T2DM). We aimed to study if OCN could improve the disorder of islet cell caused by lipotoxicity. Methods Alizarin red staining was used to investigate the mineralization. Western blotting and ELISA methods were used to measure protein expression. Immunofluorescence staining was used to investigate the protein nuclear transfer. Results High glucose and high fat inhibited the differentiation of osteoblast precursors. Overexpression of insulin receptor (InsROE) significantly promoted the Runx2 and OCN expression. The increase of insulin, Gprc6a, and Glut2 by osteoblast culture medium overexpressing insulin receptor was reversed by osteocalcin neutralizing antibody. Undercarboxylated osteocalcin (ucOC) suppressed the lipotoxic islet β-cell damage caused by palmitic acid. The FOXO1 from intranuclear to extranuclear was also significantly increased after ucOC treatment compared with the group PA. Knockdown of Gprc6a or suppression of PI3K/AKT signal pathway could reverse the upregulation of GPRC6A/PI3K/AKT/FoxO1/Pdx1 caused by ucOC. Conclusion OCN could activate the FOXO1 signaling pathway to regulate GLUT2 expression and improve the insulin secretion disorder caused by lipotoxicity.

Risk prediction of diabetes and pre-diabetes based on physical examination data.

Diabetes is a metabolic disorder caused by insufficient insulin secretion and insulin secretion disorders. From health to diabetes, there are generally three stages: health, pre-diabetes and type 2 diabetes. Early diagnosis of diabetes is the most effective way to prevent and control diabetes and its complications. In this work, we collected the physical examination data from Beijing Physical Examination Center from January 2006 to December 2017, and divided the population into three groups according to the WHO (1999) Diabetes Diagnostic Standards: normal fasting plasma glucose (NFG) (FPG < 6.1 mmol/L), mildly impaired fasting plasma glucose (IFG) (6.1 mmol/L ≤ FPG < 7.0 mmol/L) and type 2 diabetes (T2DM) (FPG > 7.0 mmol/L). Finally, we obtained1,221,598 NFG samples, 285,965 IFG samples and 387,076 T2DM samples, with a total of 15 physical examination indexes. Furthermore, taking eXtreme Gradient Boosting (XGBoost), random forest (RF), Logistic Regression (LR), and Fully connected neural network (FCN) as classifiers, four models were constructed to distinguish NFG, IFG and T2DM. The comparison results show that XGBoost has the best performance, with AUC (macro) of 0.7874 and AUC (micro) of 0.8633. In addition, based on the XGBoost classifier, three binary classification models were also established to discriminate NFG from IFG, NFG from T2DM, IFG from T2DM. On the independent dataset, the AUCs were 0.7808, 0.8687, 0.7067, respectively. Finally, we analyzed the importance of the features and identified the risk factors associated with diabetes.

Prescription Pattern and Treatment Target in Patients with Type 2 Diabetes Attending a Tertiary Health Center in Lagos

Background: The prevalence of diabetes is on the increase worldwide. Type 2 diabetes is the most common form of diabetes and is characterized by disorders of insulin action and insulin secretion; any of these two abnormalities may be the predominant feature of the disease. The aim of the study was to review the drug treatment of patients with type 2 diabetes attending a follow-up clinic. Materials and Methods: The study took place at the outpatient clinic of a tertiary health center among patients attending a follow-up clinic. The study design was a descriptive cross-sectional review of the use of antidiabetic medications among adult males and females with type 2 diabetes. Results: A total of 235 participants took part in this study. 64.3% were females; the average age of the participants was 60.7 years with an age range of 20–88 years. This study showed metformin as the most commonly prescribed medication among the participants. Almost two-thirds of the participants were diagnosed with diabetes after they had developed symptoms or complications of diabetes. The proportion of participants with fasting blood sugar at the target level was 54.5%. Conclusion: In conclusion, this study revealed that metformin is the most commonly prescribed antidiabetic medication among the participants; almost two-thirds of the participants were detected to be diabetic after they have either developed symptoms or complications of the disease. Fasting blood sugar was at target levels in more than half of the participants.

Diabetes mellitus in patients using psychotropic medications: How does it work?*

Summary Diabetes mellitus (DM) is not a single disease, but a group of diseases that are characterized by chronic hyperglycemia and risk of damage to tissues and organs. The mechanisms of its development are different and due mainly to disorders of insulin secretion or its effects. For this reason, 4 types of DM have been distinguished. One of them is a specific type of DM, determined, inter alia, by the use of certain psychotropic medications. Chronic hyperglycemia often occurs in association with some of these drugs, but in many cases it is categorized erroneously as type 2 (T2DM) or 1 (T1DM). The relationship between DM and psychiatric disorders is bi-directional, involving two mutually independent risk factors for the development of the disease. However, not all patients with a mental illness develop carbohydrate metabolism disorders, which is due to a varied diabetogenic potential and mechanisms of action of psychotropic medications. In clinical practice, questions concerning the frequency of this type of DM, risk factors of its development and hyperglycemic mechanism of psychotropic medications arise. Therefore, the aim of this article is to attempt to answer these questions. From a practical point of view, obtaining such information should allow for the development of appropriate diagnostic and therapeutic procedures.

Production and purification of ATP-sensitive potassium channel particles for cryo-electron microscopy.

ATP-sensitive potassium (KATP) channels are multimeric protein complexes made of four inward rectifying potassium channel (Kir6.x) subunits and four ABC protein sulfonylurea receptor (SURx) subunits. Kir6.x subunits form the potassium ion conducting pore of the channel, and SURx functions to regulate Kir6.x. Kir6.x and SURx are uniquely dependent on each other for expression and function. In pancreatic β-cells, channels comprising SUR1 and Kir6.2 mediate glucose-stimulated insulin secretion and are the targets of antidiabetic sulfonylureas. Mutations in genes encoding SUR1 or Kir6.2 are linked to insulin secretion disorders, with loss- or gain-of-function mutations causing congenital hyperinsulinism or neonatal diabetes mellitus, respectively. Defects in the KATP channel in other tissues underlie human diseases of the cardiovascular and nervous systems. Key to understanding how channels are regulated by physiological and pharmacological ligands and how mutations disrupt channel assembly or gating to cause disease is the ability to observe structural changes associated with subunit interactions and ligand binding. While recent advances in the structural method of single-particle cryo-electron microscopy (cryoEM) offers direct visualization of channel structures, success of obtaining high-resolution structures is dependent on highly concentrated, homogeneous KATP channel particles. In this chapter, we describe a method for expressing KATP channels in mammalian cell culture, solubilizing the channel in detergent micelles and purifying KATP channels using an affinity tag to the SURx subunit for cryoEM structural studies.

AI-based prediction for the risk of coronary heart disease among patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is one common chronic disease caused by insulin secretion disorder that often leads to severe outcomes and even death due to complications, among which coronary heart disease (CHD) represents the most common and severe one. Given a huge number of T2DM patients, it is thus increasingly important to identify the ones with high risks of CHD complication but the quantitative method is still not available. Here, we first curated a dataset of 1,273 T2DM patients including 304 and 969 ones with or without CHD, respectively. We then trained an artificial intelligence (AI) model using randomly selected 4/5 of the dataset and use the rest data to validate the performance of the model. The result showed that the model achieved an AUC of 0.77 (fivefold cross-validation) on the training dataset and 0.80 on the testing dataset. To further confirm the performance of the presented model, we recruited 1,253 new T2DM patients as totally independent testing dataset including 200 and 1,053 ones with or without CHD. And the model achieved an AUC of 0.71. In addition, we implemented a model to quantitatively evaluate the risk contribution of each feature, which is thus able to present personalized guidance for specific individuals. Finally, an online web server for the model was built. This study presented an AI model to determine the risk of T2DM patients to develop to CHD, which has potential value in providing early warning personalized guidance of CHD risk for both T2DM patients and clinicians.

Antidiabetic Effects of Arginyl-Fructosyl-Glucose, a Nonsaponin Fraction from Ginseng Processing in Streptozotocin-Induced Type 2 Diabetic Mice through Regulating the PI3K/AKT/GSK-3β and Bcl-2/Bax Signaling Pathways.

Streptozotocin- (STZ-) induced type 2 diabetes mellitus (T2DM) caused insulin secretion disorder and hyperglycemia, further causing tissue and organ damage. In recent years, studies on ginseng (Panax ginseng C. A. Meyer) and its saponins (Ginsenosides) have proved to possess antidiabetic pharmacological activities, but the mechanism of nonsaponins on STZ-induced T2DM is still unclear. Arginyl-fructosyl-glucose (AFG) is a representative nonsaponin component produced in the processing of red ginseng. The present study was designed to assess the possible healing consequence of AFG on STZ-induced T2DM in mice and also to explore its fundamental molecular contrivances. T2DM-related indexes, fasting blood glucose levels, and body weight, histological changes, biochemical considerations, biomarkers, the mRNA countenance intensities of inflammatory facts, and variations in correlated protein manifestation in adipose tissue and liver tissue were calculated. Consequences specified that AFG usage successfully amends STZ-induced insulin conflict and liver grievance in T2DM. Systematically, AFG action diminished STZ-induced oxidative stress and inflammatory responses in the liver. In addition, we demonstrated that AFG also attenuates apoptosis and insulin secretion disorders in T2DM by adjusting the PI3K/AKT/GSK3β signaling pathway. At the end, these discoveries recommend that AFG averts the development of T2DM through numerous types of machinery and proposes that AFG can also be used in order to treat T2DM in the future.

Hypoglicemic and Antioxidant Activity of Yellow Pumpkin (Curcubitamoschata) in Diabetic Rats

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia due to disorders of insulin secretion, insulin sensitivity, or both. The main mode of diabetes control can be achieved with diet, exercise, and insulin replacement therapy nor with various oral hypoglycemic drugs. Diabetes mellitus also results in disorder of the lipid profile of the body so that the cells are more susceptible to lipid peroxidation. Malondialdehyde (MDA) is formed as a result of lipid peroxidation that can be used to measure lipid peroxidized. It has been reported that the polysaccharide from the pumpkin (Cucucrbitamoschata) has hypoglycemic activity by increasing plasma insulin. This study aims to determine the activity of hypoglycemic, and the effect of hepatoprotective pumpkin in alloxan‑induced diabetic rats by 30 Rattus norvegicus, divided into 6 groups of 5 each. Group K (‑) was the negative control group without treatment, K (+) of untreated diabetic control group, TC1, TC2, TC4 were grouped with pumpkin flour with 1, 2 and 4 gram/kg bwt for 21 day by gavage, and the diabetic group given glibenclamide 0.45 mg/kg body weight. The hypoglycemic effect was determined by measuring the blood glucose level, the antioxidant effect determined by measuring the activity of AST and ALT enzymes and the serum malondialdehyde levels. The results of this study showed that the pumpkin flour had the hypoglycemic effect of lowering blood glucose level at 4 g/kg bwt doses equivalent to Glibenclamide 0.45 mg/kg bwt (p&gt; 0.05); had antioxidant activity by decreasing the activity of AST and ALT enzymes (p &lt;0.05) and decreasing malondialdehid levels in diabetic rats (p &lt;0.05).

Corrigendum to "miR-149 Negative Regulation of mafA Is Involved in the Arsenite-Induced Dysfunction of Insulin Synthesis and Secretion in Pancreatic Beta Cells".

Chronic exposure to arsenic, a potent environmental oxidative stressor, is associated with the incidence of diabetes. However, the mechanisms for arsenite-induced reduction of insulin remain largely unclear. After CD1 mice were treated with 20 or 40 ppm arsenite in the drinking water for 12 months, the mice showed reduced fasting insulin levels, a depression in glucose clearance, and lower insulin content in the pancreas. The levels of glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells isolated from arsenite-exposed mice were low compared with those for control mice. Immunohistochemistry studies showed that arsenite exposure resulted a reduction of insulin content in the pancreas of mice. Exposure of Min6 cells, a pancreatic beta cell line, to low levels of arsenite led to lower GSIS in a dose- and time-dependent fashion. Since microRNAs (miRNAs) are involved in pancreatic β-cell function and the pathogenesis of diabetes, we hypothesized that arsenite exposure activates miR-149, decreases insulin transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (mafA), and induces an insulin synthesis and secretion disorder. In arsenite-exposed Min6 cells, mafA activity was lowered by the increase of its target miRNA, miR-149. Luciferase assays illustrated an interaction between miR-149 and the mafA 3' untranslated region. In Min6 cells transfected with an miR-149 inhibitor, arsenite did not regulate GSIS and mafA expression. In control cells, however, arsenite decreased GSIS or mafA expression. Our results suggest that low levels of arsenite affect β-cell function and regulate insulin synthesis and secretion by modulating mafA expression through miR-149.

TLR4 knockout can improve dysfunction of β-cell by rebalancing proteomics disorders in pancreas of obese rats.

Studies showed that TLR4 knockout (TLR4KO) could mitigate obesity and insulin resistance induced by high-fat diet in rats. In this study, we further investigated the effects of TLR4KO on islet function and pancreatic proteomics in obese rats by high-fat diet. PA-induced lipotoxicity β-cells, SD and TLR4KO rats were used in this study. iTRAQ was used to screen out meaningful differential proteins.The protein expression level was evaluated by Western blotting; the cell apoptosis was detected by TUNEL assay. TLR4KO could reduce inflammatory and regulate body composition in obese rats, and improve β-cells function. The quantitative analysis of protein revealed that TLR4KO rebalanced proteomics disorders in pancreas of obese rats. In addition, the pathways involved in differential proteins were mainly metabolic pathways, arachidonic acid metabolism, ECM-receptor interaction, pancreatic secretion, PI3K-Akt signaling pathway, and FoxO signaling pathway. Further analysis of protein-protein interaction (PPI) revealed that Stk39 and Ass1 interacting through Mapk14-Ywhae were node proteins and participated in inflammatory response, carboxylic acid metabolic process, and small molecule metabolic process. In vitro experiments we confirmed that silencing TLR4 can inhibit PA-induced β-cell apoptosis, insulin secretion disorders, and increase Ass1 expression. While, overexpression of Ass1 in β-cell inhibited PA or LPS-induced β-cell damage. Our study confirmed that TLR4KO could improve dysfunction of β-cell, and the underlying mechanism might be involved in ebalancing proteomics disorders in pancreas, affecting the expression of Ass1.

The Relationship between Magnesium Level with Glucose Regulation and Amount of Proteinuria in Type 2 Diabetes

Diabetes Mellitus is a globally common, chronic metabolic disease. In progression of disease itself, peripheral insulin resistance and insulin secretion disorders can be observed. In addition there can be electrolyte disorders such as magnesium, calcium and iron deficiency. Magnesium levels may have significant role in the clinical course of the disease. In this study, it is aimed to observe relationship among magnesium levels glucose regulation and proteinuria. In this cross sectional study, 200 diabetic patients were examined for magnesium levels. Blood parameters and proteinuria levels were determined and the patients were divided into two groups as hypomagnesemic and normomagnesemic. Glucose levels, HbA1c and proteinuria levels were compared between groups. Of the cases (n=200), 59 (29.5 %) were male and 141 (70.5 %) were female. The frequency of hypomagnesemia was 38.5 %. The incidence of hypomagnesemia in women (46.1 %) was significantly higher than in men (20.3 %) (p=0.001). In hypomagnesemia group, glucose level (179.7 ± 60.2 mg/dL) was higher than normomagnesemia group (160.7 ± 52 mg/dL) (p=0.013). However, no statistically significant difference was observed between the groups in terms of HbA1c level. Proteinuria levels were higher in hypomagnesemia group (0.18 ±0.12 mg/mg) than normomagnesemia group (0.14±0.05 mg/mg) (p=0.013). Magnesium deficiency is a common condition in diabetic patiens and may have negative effects on glucose regulation and proteinuria. Randomized controlled trials are needed to clarify the role of magnesium in diabetic complications. Keywords: Diabetes Mellitus, magnesium, proteinuria DOI: 10.7176/JSTR/5-10-02

The Effect Of Diabetic Foot Spa On Ankle Brachial Index And Foot Sensitivity Of Diabetes Mellitus Type 2

Diabetes Mellitus (DM) is a metabolic disorder which marked by the hyperglycemia that appeared because of insulin secretion disorder and/or the increase of cellular insulin resistance. DM patients have a higher risk to experience foot problems due to blood vessels disorders causing the circulation of blood from legs is decreased. Purposed this research is diabetes could be prevented by doing a foot spa diabetic which the activities include foot exercises, warm water cleansing and massage. The method used in this study is Quays Experiment pre-post control group design. The population on this study was patients with Diabetes Mellitus Type 2 in Waru health center. The sample used was 60 people, divided into 2 groups; intervention and control group, with sampling technique of simple random sampling. The data collection was using observation sheets of diabetic foot SPA; the tool used to assess blood glucose levels was glucometer, whereas cotton, brush and needle were used to assess the foot sensitivity. The data was then analyzed with t-test. The result of the study showed that there were effecton the foot sensitivity (t=10,73, p value =0, 000) and there were effectdecrese on ankle brachial index(t=12,34, p value =0, 000). It is important for families and communities to give motivation to the diabetes mellitus patients to do diabetic foot SPA as one of alternative therapies to prevent foot complications such as foot ulcers and even amputation