Insulin Receptor Sensitivity Research Articles

Insulin injection rotation and Diabetes Mellitus nutritional management education

The management of Diabetes Mellitus (DM) involves implementing a healthy lifestyle and pharmacological interventions through the administration of anti-hyperglycemia drugs. An essential aspect of treating DM patients is insulin administration, which facilitates glucose transportation into cells. This study evaluated the effectiveness of insulin injection rotation and nutritional management education for DM.The literature search utilized the keywords "education,"AND "insulin injection," AND "nutritional management," AND "DM", ranged 2021-2023 Searches were conducted on various databases, including Proquest, NCBI, BMC, ScienceDirect, and other relevant platforms such as Google Scholar.Ten journal articles pertinent to the subject matter were identified in the study. Findings indicate that nutritional education facilitates overall health improvement in individuals with DM, contributing to maintaining average body weight and near-normal blood glucose levels. It also enhances lipid profile and insulin receptor sensitivity while being a preventive measure against acute or chronic complications such as hyperglycemia. It is noted that selecting the appropriate injection site can significantly impact patients' blood glucose levels. While it is recommended to administer injections at consistent locations, repetitive use of the same site may pose risks of side effects, such as lipodystrophy.After conducting a comprehensive review of ten journal articles, it has been concluded that insulin injection rotation and nutritional management education are effective for managing DM.

Maternal Lipid Profile Changes in Gestational Diabetes Mellitus

Introduction: Pregnancy is commonly recognized as a state of physiological and temporary insulin resistance. This condition is driven by high concentrations of steroid hormones such as progesterone, estrogens, prolactin, cortisol and placenta-derived human placental lactogen. All of these are diabetogenic and combined cause for decreased sensitivity of insulin receptors within target tissues. Women with prior GDM are at greater risk for developing hypertension, hyperlipidaemia and electrocardiogram abnormalities. Materials and Methods: seventy five patients with Gestational diabetes mellitus and 75 healthy Normal pregnant women were enrolled for the study after the institutional ethical committee’s clearance was obtained. The fasting blood samples of the study subjects were evaluated for the glucose, lipid profile, Glycated Haemoglobin (HbA1c), Malondialdehyde (MDA) and calculated BMI. Results: Lipid peroxidation is enhanced in GDM group as MDA values have elevated significantly (p < 0.0001) compared to normal pregnancy. Total cholesterol (p< 0.001) and LDL (p = 0.001) are found to be significantly higher in GDM, but there are no significant differences in triglycerides and HDL between normal and diabetic pregnant women. Obesity is observed in GDM group as their BMI (p < 0.001) is significantly higher than that of the control group. Conclusions: It was found that GDM is associated with hyperlipidaemia as evidenced by the significantly elevated total cholesterol and LDL concentrations. Obesity and lipid peroxidation are significantly high in GDM. Keywords: Gestational diabetes mellitus, HbA1c, lipid profile, lipid peroxidation, BMI.

Sialic acids cleavage induced by elastin-derived peptides impairs the interaction between insulin and its receptor in adipocytes 3T3-L1.

The insulin receptor (IR) plays an important role in insulin signal transduction, the defect of which is believed to be the root cause of type 2 diabetes. In 3T3-L1 adipocytes as in other cell types, the mature IR is a heterotetrameric cell surface glycoprotein composed of two α subunits and two β subunits. Our objective in our study, is to understand how the desialylation of N-glycan chains, induced by elastin-derived peptides, plays a major role in the function of the IR. Using the 3T3-L1 adipocyte line, we show that removal of the sialic acid from N-glycan chains (N893 and N908), induced by the elastin receptor complex (ERC) and elastin derived-peptides (EDPs), leads to a decrease in the autophosphorylation activity of the insulin receptor. We demonstrate by molecular dynamics approaches that the absence of sialic acids on one of these two sites is sufficient to generate local and general modifications of the structure of the IR. Biochemical approaches highlight a decrease in the interaction between insulin and its receptor when ERC sialidase activity is induced by EDPs. Therefore, desialylation by EDPs is synonymous with a decrease of IR sensitivity in adipocytes and could thus be a potential source of insulin resistance associated with diabetic conditions.

Metabolomic signature between diabetic and non-diabetic obese patients: A protocol for systematic review.

Type 2 diabetes mellitus (T2DM) is a chronic and progressive condition defined by hyperglycemia caused by abnormalities in insulin production, insulin receptor sensitivity, or both. Several studies have revealed that higher body mass index (BMI) is associated with increasing risk of developing diabetes. In this study, we perform a protocol for systematic review to explore metabolite biomarkers that could be used to identify T2DM in obese subjects. The protocol of this review was registered in PROSPERO (CRD42023405518). Three databases, EMBASE, PubMed, and Web of Science were selected to collect potential literature from their inceptions to July December 2023. Data for collection will include title, authors, study subjects, publication date, sample size, detection and analytical platforms, participant characteristics, biological samples, confounding factors, methods of statistical analysis, the frequency and directions of changes in potential metabolic biomarkers, and major findings. Pathway analysis of differential metabolites will be performed with MetaboAnalyst 5.0 based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database. The results of this systematic review will be published in a peer-reviewed journal. This systematic review will summarize the potential biomarkers and metabolic pathways to provide a new reference for the prevention and treatment of T2DM in obese subjects.

Effect of Vitamin D on Retinoblastoma Protein in Prediabetic Individuals.

About 50.8 million people were diagnosed with diabetes in 2011; the count has increased by 10 million in the last five years. Type-1 diabetes could occur at any age, but predominantly in children and young adults. The risk of developing type II diabetes mellitus in the offspring of parents with DM II is 40% if one parent has DM II and approaches 70% if both parents have DM II. The process of developing diabetes from normal glucose tolerance is continuous, with insulin resistance being the first stage. As prediabetes progresses slowly to DM II, it may take approximately 15-20 years for an individual to become diabetic. This progression can be prevented or delayed by taking some precautions and making some lifestyle amendments, e.g., reducing weight by 5-7% of total body weight if obese, etc. Retinoblastoma protein is one of the pocket proteins that act as crucial gatekeepers during the G1/S transition in the cell cycle. A loss or defect in single- cell cycle activators (especially CDK4 and CDK6) leads to cell failure. In diabetic or stress conditions, p53 becomes a transcription factor, resulting in the transactivation of CKIs, which leads to cell cycle arrest, cell senescence, or cell apoptosis. Vitamin D affects insulin sensitivity by increasing insulin receptors or the sensitivity of insulin receptors to insulin. It also affects peroxisome proliferator-activated receptors (PPAR) and extracellular calcium. These influence both insulin resistance and secretion mechanisms, undertaking the pathogenesis of type II diabetes. The study confines a marked decrement in the levels of random and fasting blood glucose levels upon regular vitamin D intake, along with a significant elevation of retinoblastoma protein levels in the circulatory system. The most critical risk factor for the occurrence of the condition came out to be family history, showing that patients with first-degree relatives with diabetes are more susceptible. Factors such as physical inactivity or comorbid conditions further aggravate the risk of developing the disease. The increase in pRB levels caused by vitamin D therapy in prediabetic patients directly influences blood glucose levels. pRB is supposed to play a role in maintaining blood sugar levels. The results of this study could be used for further studies to evaluate the role of vitamin D and pRB in regeneration therapy for beta cells in prediabetics.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: diagnostic and therapeutic aspects. Review

The increase in the prevalence of non‑alcoholic fatty liver disease (NAFLD) occurs in parallel with the global epidemic of obesity and type 2 diabetes mellitus (T2DM) in the world. T2DM is an independent risk factor for the development of NAFLD. At the same time, researchers found that patients diagnosed with NAFLD have a two‑fold increased risk of developing T2DM. NAFLD is encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. NASH is an aggressive form of NAFLD, associated with an increased risk of liver and non‑liver‑related mortality. Liver‑biopsy remains the gold standard for diagnosis, but the majority of patients liver damage can be diagnosed accurately by noninvasive methods.
 The presence of NAFLD in a patient with T2DM makes it difficult to achieve adequate glycemic control, deepens the manifestations of insulin resistance and atherogenic dyslipidemia, increases the risk of serious cardiovascular events and chronic kidney disease. Lifestyle modification and treatment of concomitant T2DM should be undertaken in all patients with NAFLD. To reduce the severity of liver steatosis, weight reduction by 3—5% is necessary, to reduce the inflammatory‑necrotic process, a more significant reduction may be required — up to 10% within 6—12 months. Physical activity increases the sensitivity of insulin receptors, and in combination with diet leads to a significantly significant improvement in biochemical and histological indicators in patients with NAFLD. Early identification and management of patients with intensive dietary and lifestyle modification are essential to prevent the development of advanced liver disease and its complications. Pharmacological therapy should be administered to patients with NASH purposed on the fibrosis inhibition, especially in case of the established predictors of high risk of disease progression (age >50 years, metabolic syndrome, T2DM, or increase in the activity of alanine aminotransferase), as well as to the patients with active NASH with high inflammatory activity.
 At the congress of the European Association for the Study of the Liver (EASL), which took place in Vienna on June 21—24, 2023, a new classification and nomenclature of NAFLD was adopted. It was proposed to replace the term «non‑alcoholic fatty liver disease» to the term «metabolic dysfunction‑associated steatotic liver disease» (MASLD). This diagnosis is established in patients with confirmed steatosis of the liver and one of five cardiometabolic risk factors: obesity, T2DM, insulin resistance, hyperlipidemia, atherosclerosis. The concept of «non‑alcoholic steatohepatitis» (NASH) has been changed to the concept of «metabolic dysfunction‑ associated steatohepatitis» (MASH). Coordination of the views of international and domestic experts in the field of studying this pathology will be important for clinical practice and scientific research.

Insulin regulates human pancreatic endocrine cell differentiation in vitro

ObjectiveThe consequences of mutations in genes associated with monogenic forms of diabetes on human pancreas development cannot be studied in a time-resolved fashion in vivo. More specifically, if recessive mutations in the insulin gene influence human pancreatic endocrine lineage formation is still an unresolved question. MethodsTo model the extremely reduced insulin levels in patients with recessive insulin gene mutations, we generated a novel knock-in H2B-Cherry reporter human induced pluripotent stem cell (iPSC) line expressing no insulin upon differentiation to stem cell-derived (SC-) β cells in vitro. Differentiation of iPSCs into the pancreatic and endocrine lineage, combined with immunostaining, Western blotting and proteomics analysis phenotypically characterized the insulin gene deficiency in SC-islets. Furthermore, we leveraged FACS analysis and confocal microscopy to explore the impact of insulin shortage on human endocrine cell induction, composition, differentiation and proliferation. ResultsInterestingly, insulin-deficient SC-islets exhibited low insulin receptor (IR) signaling when stimulated with glucose but displayed increased IR sensitivity upon treatment with exogenous insulin. Furthermore, insulin shortage did not alter neurogenin-3 (NGN3)-mediated endocrine lineage induction. Nevertheless, lack of insulin skewed the SC-islet cell composition with an increased number in SC-β cell formation at the expense of SC-α cells. Finally, insulin deficiency reduced the rate of SC-β cell proliferation but had no impact on the expansion of SC-α cells. ConclusionsUsing iPSC disease modelling, we provide first evidence of insulin function in human pancreatic endocrine lineage formation. These findings help to better understand the phenotypic impact of recessive insulin gene mutations during pancreas development and shed light on insulin gene function beside its physiological role in blood glucose regulation.

Results of Phase III Clinical Trial: a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Direkord in Ischemic Stroke Patients in Early Recovery Period

Direkord is an original drug containing the active substance of dicholine succinate, which improves the sensitivity of insulin receptors in neurons to insulin. The aim of this work was to evaluate the efficacy and safety of the drug in ischemic stroke patients in the early recovery period. In total, 160 patients after the first ischemic stroke in the carotid system, confirmed by computed or magnetic resonance imaging, with a stroke duration from 3 weeks to 2 months, mean age 63.2±8.4 years, were randomized into two treatment groups. The first group (n=80) received Direkord intramuscularly at a dose of 600 mg/day for two weeks; the second group (n=80) received a placebo. Treatment response was defined as an improvement in neurological status, functional status, and cognitive function of the patients: at least a two-fold decrease in the total NIHSS score, the total Barthel score ≥ 95, and the total MoCA score ≥ 26. The analysis of the primary endpoint of the study using exact Fisher’s test showed that Direkord was statistically significantly superior to the placebo (p=0.017) in the number of patients who responded to the therapy — 23.7 and 8.7% of patients in groups, respectively. The secondary end point analysis revealed a statistically significant superiority of Direkord over the placebo in reducing neurological deficits on the NIHSS scale (p=0.004), on the Rankin scale (p=0.0357), and on the CGI-I (p<0.001) and PGI-I (p<0.001) global clinical impression scales. Direkord has a good safety profile; thus, no statistically significant differences were found with the placebo in any of the safety parameters, including the number of adverse events, vital signs, laboratory parameters, and ECG. Overall, Direkord is statistically significantly more effective than placebo in recovering function and daily activities after ischemic stroke.

SELF-MANAGEMENT DIET AND RANDOM PLASMA GLUCOSE CONTROL OF PATIENT WITH TYPE 2 DIABETES MELLITUS AT PUSKESMAS ALUN-ALUN GRESIK

Background: Diabetes Mellitus (DM) is a non-communicable metabolic disease characterized by the pancreas not being able to produce insulin and a decrease in insulin receptor sensitivity. Epidemiological data show the prevalence of type 2 diabetes mellitus is high in Indonesia and estimated to increase by more than 2.5 times in 2030 compared to 2020. Several factors play an important role in the development and management of diabetes cases, including the management of a good independent diet. People with DM who do not pay attention to their diet can trigger complications and disability. Objective: This study aims to determine the correlation between independent diet management and blood sugar control in patients with type 2 diabetes mellitus. Methods: This study used an observational analytic method with a cross sectional design. The sampling technique was consecutive sampling. Self-management assessment of diet used the Self-Management Diabetic Diet Questionnaire (SMBDQ) which has been adjusted and tested for validity and reliability. Blood sugar measured using a glucometer. Data processing was conducted using Kendall's tau C with a significance level of 95% (α=0.05). Results: There was 79 respondents. There was a correlation with a significance value (P= 0.002) with a low correlation (τ=0.255) between independent diet management and current blood sugar control in patients with type 2 diabetes mellitus. Conclusion: Independent diet management has a significant correlation with blood sugar control in patients type 2 diabetes mellitus. Keywords: Diabetes mellitus, independent diet management, Random Plasma Glucose, Self-Management Diabetic Diet Questionnaire.

Phase II Clinical Trial of Direkord: Randomized, Double-Blind, Placebo-Controlled, Parallel Group, and Prospective Studies to Select Optimal Dosage and to Study the Efficacy, Safety, and Tolerability in Ischemic Stroke Patients in the Early Recovery Period

Direkord is an original drug containing the active substance of dicholine succinate, which improves the sensitivity of insulin receptors in neurons to insulin. The aim of the work was to select an optimal dosage and to study the efficacy, safety, and tolerability of Direkord, a solution for intramuscular injection, in ischemic stroke patients in the early recovery period. In total, 132 patients after the first ischemic stroke in the carotid system, confirmed by computed or magnetic resonance imaging, with the stroke remoteness from 3 weeks to 2 months and the mean age of 64.35±8.03 years, were randomized into three treatment groups. Patients in the first (n=44) and second (n=44) groups received Direkord intramuscularly for two weeks at a dose of 400 mg/day and 600 mg/day, respectively. Patients in the third group received placebo. The treatment response was assessed in terms of improved neurological status, functional state, and cognitive functions, including at least a two-fold decrease in the total score on the NIHSS scale, the total score on the Barthel scale ≥95, and the total score on the MoCA scale ≥26. Four weeks after the onset of the study, 34.1, 43.2, and 18.2% of the patients responded to therapy in the first, second, and third group, respectively. An analysis based on the Fisher’s exact test revealed a statistically significant difference between the groups (p=0.036). These results suggest that Direkord is statistically and clinically significantly superior to placebo at a two-week intramuscular therapy at a dose of 600 mg/day in patients with ischemic carotid stroke in the early recovery period. The safety profile of Direkord when used in various therapy regimens does not differ from that of placebo. The phase III study should confirm the preliminary results obtained in the current work.

Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Hyperandrogenism, hyperinsulinism and insulin resistance (IR) are the main drivers of clinical, metabolic and reproductive phenotypes of PCOS. In adolescence, the cornerstones of PCOS treatment are lifestyle and dietary interventions. In particular, the quality and quantity of carbohydrates introduced with the diet play a crucial role in the benefits of diet on PCOS. Recently, the ketogenic diet (KD) has attracted significant interest for the treatment of IR and for the control of carbohydrate metabolism, which has proven to be beneficial for several dysmetabolic conditions, including PCOS. The goal of the KD is to induce a fasting-like metabolism with production of chetonic bodies. Ketosis is a good regulator of calorie intake and mimics the starvation effect in the body, leading to body weight control and consequent metabolism. Additionally, during ketogenesis, insulin receptor sensitivity is also promoted. We proposed a broad overview of the available literature regarding KD indications and considered its metabolic benefits useful for improving PCOS management. The reported data support that a low-calorie ketogenic diet (LCKD) plays a positive role as a regulator of control weight, IR, glucose and lipid homeostasis and hormonal profile. Unfortunately, the evidence concerning the benefits of the very LCKD in adolescents with PCOS and excessive body weight is still numerically scarce. Further studies are necessary to understand whether these effects are due to weight loss or to the nutritional characteristics of this diet. Considering the long-term consequences of PCOS, it is crucial to detect the prospects of nutritional interventions to protect fertility, starting in adolescence.

#3932 INSULIN RESISTANCE IN PEDIATRIC CKD PATIENTS

Abstract Background and Aims Pediatric chronic kidney disease (CKD) is associated with disturbance of glucose metabolism & insulin receptor sensitivity leading to impaired glucose tolerance & insulin resistance (IR), which are potential risk factors for cardiovascular disease (CVD). Hyperinsulinemia and IR are not extensively investigated in children with CKD, especially in different stages of CKD. The aim of our study was to detect hyperinsulinemia & IR in pediatric CKD patients. Method A total of 87 children and adolescents; 58 with chronic kidney disease (CKD); (29 CKD stage 2-4, pre-dialysis group & 29 CKD stage 5 on regular hemodialysis, CKD5d group) & 29 age & gender matched controls were enrolled in the current cross-sectional study. Homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin & glucose, where IR was considered if HOMA-IR was 4.39. Results Fasting insulin & glucose hadn't significantly changed between CKD patients & controls (p = 0.7, 0.3 respectively), while IR represented by HOMA-IR was found in a total of 11 (12.6%) CKD patients (6, 6.89% CKD5d & 5, 5.74% CKD 2-4) with no significant difference between pre-dialysis & dialysis groups (p>0.05), while it was significant with controls (p = 0.039), meanwhile, the total means of HOMA-IR between were no statistically significant between all CKD patients & (p = 0.64). HOMA-IR correlated positively to dialysis durations (p = <0.001, <0.001 respectively), but hadn't changed with BMI. Conclusion Pre-dialysis & dialysis CKD pediatric patients are at a high risk of IR & hence CVD. CKD & dialysis durations are independent risk factors for IR.

Redox-stress response resistance (RRR) mediated by hyperoxidation of peroxiredoxin 2 in senescent cells.

Aging is closely related to redox regulation. In our previous work, we proposed a new concept, "redox-stress response capacity (RRC)," and found that the decline in RRC was a dynamic characteristic of aging. However, the mechanism of RRC decline during aging remains unknown. In this study, using the senescent human fibroblast cell model and Caenorhabditis elegans model, we identified that peroxiredoxin 2 (PRDX2), as a hydrogen peroxide (H2O2) sensor, was involved in mediating RRC. PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C. elegans also showed decreased RRC. The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells. Moreover, the level of PRDX2 hyperoxidation also increased in old C. elegans. Simultaneous overexpression of both PRDX2 and sulfiredoxin (SRX) rescued the reduced RRC and delayed senescence. The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity, resulting in the decreased cellular response to H2O2, which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity. Treatment of young cells with a high level of H2O2 to induce a higher level of PRDX2-SO3 resulted in mimicking the RRC decline in senescent cells, which is also similar to a model of insulin resistance induced by high levels of insulin. All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells, we named it redox-stress response resistance, RRR. RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.

Magnesium and insulin leaf combination on glucose, low-density lipoprotein and malondialdehyde levels in wistar rats with diabetes mellitus

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia due to impaired insulin secretion, insulin receptor sensitivity and/or both. Hyperglycemia can trigger oxidative stress conditions that can increase the risk of micro and macrovascular complications. Preventive efforts need to be done such as giving supplements and traditional therapies that have low side effects, namely magnesium and insulin leaves. This research is experimental type with post test only control group. The samples in this study were 30 male wistar rats weighing 170-300g which had healthy conditions adapted for 7 days, given standard feed and given ad libitum drinking water. The results showed that the glucose level in the treatment group 3 when compared to the negative control group had a percentage decrease of 26.49%. LDL and MDA levels were lower in the combination treatment group of magnesium and insulin leaves when compared to the negative control group. The ANOVA results showed that there was a significant difference between the groups in the glucose test results (p < 0.05), and there was no significant difference between the groups in the LDL and MDA results (p > 0.05). The conclusion of this study was that the best results when compared to negative controls were the combination of magnesium at a dose of 300 mg and insulin leaves at a dose of 300 mg/KgBB had a decreased percentage of LDL levels by 52.38% and MDA levels of 29.11%, while for glucose levels the combination of magnesium doses 300 mg and insulin leaves 75 mg/KgBW had a percentage reduction of 26.49%

A healthy lifestyle of the diabetic sufferer to avoid the risk of complications: Literature Review

Diabetes Mellitus (DM) is a chronic disease with high blood sugar levels in the blood. DM can cause complications of various diseases because the body can not use blood sugar in the blood cannot be used. The number of DM sufferers, both in the world and in Indonesia, continues to increase from time to time, so this disease is a scourge for everyone. Writing this paper aims to discuss the healthy lifestyle of diabetics to avoid the risk of complications. The most severe disorder of this disease is a chronic metabolic disorder because the pancreas does not produce enough insulin hormone, which has the principal role in regulating and controlling glucose metabolism into energy. Over time, diabetes can interfere with the function of human organs. For example, some organs work improperly, and some should be amputated. One of the most effective efforts to keep blood sugar levels stable is dietary compliance in people with diabetes mellitus has role function. The impact of dietary regulation is maintaining normal-body weight, reducing systolic and diastolic blood pressure, lowering blood glucose levels, improving lipid profiles, increasing insulin receptor sensitivity, and improving the blood coagulation system. This disease requires continuous medical care by carrying out independent health management in patients to prevent acute complications and reduce the risk of long-term complications. It is principal to adopt a healthy lifestyle for diabetic patients in a frame to anticipate the risk of complications.

Adipose Insulin Resistance Associates With Dyslipidemia Independent of Liver Resistance and Involves Early Hormone Signaling.

Adipose tissue insulin resistance is linked to altered plasma levels of triglycerides and HDL (high-density lipoprotein)-cholesterol. However, its degree of independence from liver resistance and different metabolic traits (lipolysis, lipogenesis) effected is not clear and was presently investigated. In 3290 adult subjects, plasma levels of triglycerides and HDL-cholesterol were cross-sectionally measured and related to interindividual variations in measures of insulin resistance in the liver (homeostasis mode assessment of insulin resistance index) or adipose tissue (Adipo-IR index). In subgroups, insulin-induced antilipolysis and lipogenesis in isolated subcutaneous fat cells (n=578) were determined alongside global adipose tissue gene expression (n=132). Using linear regression, homeostasis mode assessment of insulin resistance and Adipo-IR strongly correlated with the plasma lipids explaining 33% of the variations in triglycerides. Together with other variables (age, sex, body mass index, cardiometabolic disorders, nicotine use, ethnicity, and physical activity) in multiple regression, homeostasis mode assessment of insulin resistance, and Adipo-IR each remained an important regressor for triglycerides and HDL-cholesterol (P<0.0001). In fat cells, half-maximum effective concentration but not maximum effect of insulin on antilipolysis and lipogenesis contributed independently to variations in triglycerides and HDL-cholesterol (P=0.001 or lower). This was linked to expression of the insulin receptor, insulin receptor substrate-1, and AKT serine/threonine kinase 2 in adipose tissue. Markers of insulin resistance in the liver and adipose tissue each associate strongly, and independently of each other, to elevated triglycerides and decreased HDL levels. At the fat cell, early insulin receptor signaling and sensitivity, but not maximum insulin action contributes to the variations in circulating triglycerides and HDL-cholesterol.

DIFFERENCES IN BLOOD SUGAR LEVELS BEFORE AND AFTER MORNING AND AFTERNOON WALK IN TYPE II DIABETES MELITUS PATIENTS AT BABAKANSARI PUSKESMAS

Diabetes Mellitus (DM) is a non-communicable disease which causes an increase in blood sugar levels and is at risk of causing disease complications. Walking is done to increase the sensitivity of insulin receptors. Blood vessels in the afternoon are more vasodilated than in the morning due to the effects of circadian rhythms which affect hormone action. This study aims to determine the difference in the average value of blood sugar levels before and after walking in the morning and afternoon in patients with type II DM. The research design used was a preexperiment with a pretest-posttest two group design approach. The sample of 20 respondents who are divided into 2 groups, namely the morning group of 10 people and the afternoon group of 10 people, with purposive sampling. The results of this study showed that the amount of decrease in blood sugar levels in the morning group was 31.6 mg/dL and the amount of decrease in blood sugar levels in the afternoon group was 43.5 mg/dL. The results of statistical tests in the morning group obtained a value of p = 0.007 (p &lt;0.05) and in the afternoon group obtained a value of p = 0.005 (p &lt;0.05). The results showed that the afternoon group was more effective in reducing average blood glucose levels as a result of vasodilatation of blood vessels which is influenced by circadian rhythms compared to the morning group, so it can be concluded that there are differences in blood sugar levels before and after walking in the morning and in the afternoon in patients with type II DM. Therefore it is advisable to walk, especially in the afternoon which can lower blood sugar levels more for type II DM sufferers in an effort to control blood sugar levels.

Association between insulin, glucagon, high sensitive c-reactive protein, insulin resistance with visceral adipose tissue-derived serine protease inhibitor (VASPIN) in obese population

Background: Obesity is an inflammatory condition that results in an increase in high sensitive C-Reactive Protein (hs-CRP), a risk for insulin resistance (IR). Vaspin has the effect of increasing insulin receptor sensitivity and on the other hand is a compensatory response to insulin resistance, one of which is measured by homeostasis models assessment-insulin resistance (HOMA-IR). This study was an analytical cross-sectional observational design, to determine the association between insulin, glucagon, CRP, and HOMA-IR levels with serum vaspin in obesity. Method: This study is an analytical study with a cross-sectional design. Criteria of inclusion were subjects in the range 18-60 years Denpasar citizen with BMI above 25 kg/m2 and willing to be involved in this study, while exclusion criteria were with either chronic conditions or acute inflammation such as infection, cancer, tumor, or chronic disease which is altered and threatening life. Correlation tests using spearman analysis. Results: From 131 obese subjects in this study, there were 72 (55%) men and 59 (45%) women. Median age: 33 (22-57) years, fasting insulin: 8.90 (2.20-74.50) ìIU/mL, glucagon: 48.10 (7.58-293.90) pq/mL, hs-CRP: 1.90 (0.20-9.50) mg/L, HOMA-IR: 2 (0.50-23.15), and vaspin levels: 0.16 (0.04-1.46) ng/mL. There was a significant positive correlation between HOMA-IR, insulin and glucagon with vaspin (r = 0.20, p = 0.020; r = 0.20, p = 0.022; and r = 0.28, p = 0.001), and a significant negative correlation between hs-CRP and vaspin (r = -0.24, p = 0.005) in obesity. In the path analysis, there was a direct and total negative effect of hs-CRP on vaspin (coefficient = -0.19; p = 0.027 and coefficient = -0.02; p = 0.038). Conclusion: This study shows a positive association between insulin, glucagon, and HOMA-IR with serum vaspin, while CRP is negatively associated with serum vaspin in obesity.

Falling Short: The Contribution of Central Insulin Receptors to Gait Dysregulation in Brain Aging.

Insulin resistance, which manifests as a reduction of insulin receptor signaling, is known to correlate with pathological changes in peripheral tissues as well as in the brain. Central insulin resistance has been associated with impaired cognitive performance, decreased neuronal health, and reduced brain metabolism; however, the mechanisms underlying central insulin resistance and its impact on brain regions outside of those associated with cognition remain unclear. Falls are a leading cause of both fatal and non-fatal injuries in the older population. Despite this, there is a paucity of work focused on age-dependent alterations in brain regions associated with ambulatory control or potential therapeutic approaches to target these processes. Here, we discuss age-dependent alterations in central modalities that may contribute to gait dysregulation, summarize current data supporting the role of insulin signaling in the brain, and highlight key findings that suggest insulin receptor sensitivity may be preserved in the aged brain. Finally, we present novel results showing that administration of insulin to the somatosensory cortex of aged animals can alter neuronal communication, cerebral blood flow, and the motivation to ambulate, emphasizing the need for further investigations of intranasal insulin as a clinical management strategy in the older population.

POTENSI SIANIDIN POLY(LACTIC-CO-GLYCOLIC ACID)-POLYETHYLEN GLYCOL YANG DIMODIFIKASI FUSED FOLLICLE UNTUK MENINGKATKAN SENSITIVITAS DAN SEKRESI INSULIN DALAM MENANGANI PENYAKIT DIABETES MELITUS TIPE 2

ABSTRACT&#x0D; Introduction: Type 2 diabetes mellitus is one of the four priority non-communicable diseases according to WHO. WHO data in 2015 showed that as many as 415 million people in the world suffer from type 2 diabetes mellitus. Even in Indonesia in 2013, the prevalence of people with diabetes has increased to 6.9%. Currently, the most common treatment for type 2 diabetes mellitus is the administration of metformin. However, long-term administration will cause lactic acidosis and kidney damage. Because of this, new alternatives are needed that minimize the side effects, for example by using herbal ingredients. Cyanidin is a natural flavonoid that has the effect of increasing insulin sensitivity and secretion.&#x0D; &#x0D; Discussion: Cyanidin has the potential to increase insulin receptor sensitivity and increase insulin secretion. To increase insulin sensitivity, cyanidin can inhibit the downregulation of Glut4 expression and decrease the level of RBP 4 expression. As an increase in insulin secretion Cyanidin increases the expression of GLUT2, Kir6.2, and Cav1.2 genes that play a role in insulin secretion. Unfortunately, Cyanidin has low bioavailability and is unstable. Therefore, Cyanidin encapsulation will increase the availability of cyanidin in the blood and is easily concentrated into pancreatic cells&#x0D; Conclusion: The Fc-modified Cyanidin PLGA-PEG combination has the potential to be a new alternative in the treatment of type 2 diabetes mellitus&#x0D; Keywords: Type 2 Diabetes Mellitus, Cyanidin, Fc-modified Cyanidin PLGA-PEG