Effects of SGLT2 Inhibitors on Atherosclerosis: Lessons from Cardiovascular Clinical Outcomes in Type 2 Diabetic Patients and Basic Researches

Atherosclerosis-caused cardiovascular diseases (CVD) are the leading cause of mortality in type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective oral drugs for the treatment of T2DM patients. Multiple pre-clinical and clinical studies have indicated that SGLT2 inhibitors not only reduce blood glucose but also confer benefits with regard to body weight, insulin resistance, lipid profiles and blood pressure. Recently, some cardiovascular outcome trials have demonstrated the safety and cardiovascular benefits of SGLT2 inhibitors beyond glycemic control. The SGLT2 inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin reduce the rates of major adverse cardiovascular events and of hospitalization for heart failure in T2DM patients regardless of CVD. The potential mechanisms of SGLT2 inhibitors on cardioprotection may be involved in improving the function of vascular endothelial cells, suppressing oxidative stress, inhibiting inflammation and regulating autophagy, which further protect from the progression of atherosclerosis. Here, we summarized the pre-clinical and clinical evidence of SGLT2 inhibitors on cardioprotection and discussed the potential molecular mechanisms of SGLT2 inhibitors in preventing the pathogenesis of atherosclerosis and CVD.

The Effectiveness of Virgin Coconut Oil on the Decrease of Blood Glucose Levels on Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM) was medical complication that occurs during pregnancy and caused preterm labor. Efforts reduce blood glucose levels and improve pancreatic performance must be safe both for mother and fetus. The research aimed to prove VCO can reduce blood glucose levels in GDM. The research design was quasi-experimental with one group pre-test and post-test. The research started on March to September 2020. The population was pregnant mother with GDM from two hospitals in Mojokerto East Java. The sample was 46 respondents with purposive sampling. The treatment given was VCO at a dose of 5 ml, 6 times a day and lowcarb diet. The instrument used to measure the fasting blood glucose was glucose stick. The data was analyzed with paired t-test. The result showed blood glucose levels before intervention average of 155.19 mg/dL and after 153.50 mg/dL. The t-test value 14.442 and p value 0.000 which meant that VCO and low carb diet was more effective in reducing blood glucose levels on GDM. The administration of VCO with a low carb diet is an effort to restrict glucose intake in the body without hypoglycemia. It is safe to use for both mother and fetus as an alternative non-pharmacological therapy on GDM and prevent preterm labor

Molecular Docking of Mangostin and Sinensetin Derivatives on SUR1-Pancreatic KATP Channel Target as Antidiabetic

Background: Diabetes Mellitus (DM) is a complex chronic disease characterized by increased blood glucose. The incidence of this disease is rising, especially type 2 diabetes which is caused by insulin resistance in the body. SUR1-Pancreatic KATP Channel is a receptor as an antidiabetic target because its inhibition process can increase insulin production so that it can reduce blood glucose in people with type 2 diabetes. Objective: This study aims to identify the in-silico activity of the SUR1-Pancreatic KATP Channel macromolecules. Methods: Identification of macromolecular binding sites using Protein Plus software, then carried out molecular docking using AutoDock software, where the formed molecular interactions are further identified using the BIOVIA Discovery Studio software. Results: After determining the macromolecular binding site, the RMSD value was 1.253, allowing for further molecular docking. Molecular docking showed that the Ligands of mangostin (α, β, γ-mangostin) and sinensetin derivatives had a good affinity, namely α-mangostin -6,31 kcal/mol; β-mangostin -5.78 kcal/mol; γ-mangostin -6.17 kcal/mol and sinensetin -4.75 kcal/mol. Conclusion: The affinity sequence in the docking process for the SUR1 KATP channel macromolecules is α-mangostin > γ-mangostin > β-mangostin > sinensetin. The highest affinity for the docking process on the macromolecule SUR1 KATP channel was α-mangostin with a value of ΔG -6.31 kcal/mol Ki 23.65 μM.

Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes

GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound 11b showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, 11b showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound 11b could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound 11b might be a promising drug candidate for the treatment of T2DM.

Immediate effect of a meditation technique on blood glucose, state anxiety and relaxation in patients with type 2 diabetes: a pilot randomized crossover study

Objectives Type 2 Diabetes Mellitus (T2DM) is a major burden on global health and economy. Various Yogic techniques are found to be beneficial in the management of T2DM. Mind Sound Resonance Technique (MSRT) is one of the yoga-based meditation techniques observed to be effective in clinical settings. Methods Thirty-two patients with T2DM were randomized to either MSRT or supine rest (SR) sessions on two separate days separated by a washout period of one day. Fasting blood glucose levels were measured before and immediately after the sessions. State anxiety and subjective feeling of relaxation were assessed using Spielberg’s state anxiety inventory (STAI) and Visual Analogue Scale (VAS) respectively. Results There were significant differences between MSRT and SR groups in fasting blood glucose (p=0.019), STAI scores (p<0.001) and subjective relaxation (p<0.001). Within group analyses revealed significant reductions (p<0.001) in fasting blood glucose and STAI scores, along with an increase in subjective relaxation following the practice of MSRT, whereas, non-significant changes were found following the SR session. Conclusions A single session of MSRT was found to reduce blood glucose levels and state anxiety along with enhanced relaxation when compared to SR.

Cupping Therapy Benefit in Glucose Blood Level

Some Muslims have used cupping therapy and occupies a popular position among other alternative therapeutic methods. Modern medical research evidence also confirms the benefits of the therapy recommended by the Prophet. Many medical experts know the efficacy of cupping therapy in treating disease. According to the International Diabetes Federation (IDF), in 2013, Indonesia was ranked seventh with diabetes. Cupping therapy plays a role in stimulating blood circulation in the muscles, thereby increasing the metabolism of nutrients and glucose consumption by the muscles. The increased sensitivity of insulin receptors was helping to reduce blood glucose levels. This effect is like the effect of exercise and physical activity on blood glucose levels. This study aims to determine the effect of cupping therapy on blood glucose levels.

AKTIVITAS ANTIDIABETES EKSTRAK ETANOL DAUN BELIMBING BESI (Averhhoa carrambola) PADA MENCIT (Mus musculus)

Many antioxidant compounds, flavonoids, and saponins are contained in starfruit leaves (Averrhoa carambola). The purpose of this study was to determine the antidiabetic activity of star fruit extract in mice. This study used a completely randomized design (CRD) with 6 treatments, namely P1 (aquadest without alloxan) as a negative control, P2 (aquadest with alloxan) as a positive control, P3 (metformin 500 mg / kgBB), P4 (alloxan + ethanol extract of star fruit leaves. 100 mg / kgBB), P5 (alloxan + ethanol extract of star fruit leaves 150 mg / kgBB), P6 (alloxan + ethanol extract of star fruit leaves 200 mg / kgBB). The starfruit leaf extract was made using the maceration method. In order for experimental animals to become diabetic, alloxan is used at a dose of 120 mg / kgBW which is injected intramuscularly into the thigh muscles. After the experimental animals were diabetic, We were given ethanol extract of starfruit leaves according to the experimental design, starting from day 7th to day 21st. Blood glucose levels are measured with a glucometer every week. The results showed that the best decrease in blood glucose levels occurred in the first week and the second week. In the first week, the metformin treatment was able to reduce blood glucose by 88.4%, while the ethanol extract treatment of star fruit leaves at a dose of 200 mg / kg BW was able to reduce blood glucose levels by 60%. The ethanol extract of star fruit leaves has antidiabetic activity. Keywords: mice, diabetes mellitus, blood glucose, starfruit leaves.

A HYPOMETABOLIC DEFENSE STRATEGY AGAINST PLASMODIUM INFECTION

SUMMARYHypoglycemia is a clinical hallmark of severe malaria, the often-lethal presentation of Plasmodium falciparum infection of humans. Here we report that mice reduce blood glucose levels in response to Plasmodium infection via a coordinated response whereby labile heme, an alarmin produced via hemolysis, induces anorexia and represses hepatic glucose production (HGP). While protective against unfettered immune-mediated inflammation, organ damage and anemia, when sustained over time heme-driven repression of HGP can progress towards hypoglycemia, compromising host energy expenditure and thermoregulation. This hypometabolic state arrests the development of asexual stages of Plasmodium spp., which undergo pyknosis and develop mitochondrial dysfunction. In response, Plasmodium activates a transcriptional program reducing its virulence and inducing sexual differentiation towards the production of transmissible gametocytes. We infer that malaria-associated hypoglycemia represents a trade-off of an evolutionarily conserved defense strategy restricting Plasmodium spp. from accessing host-derived glucose and balancing parasite virulence and transmission.

Renoprotective Effects of Incretin-Based Therapy in Diabetes Mellitus

Glucagon-like peptide-1 (GLP-1) receptor agonists are recently discovered antidiabetic drugs with potent hypoglycemic effects. Among different mechanisms of activity, these compounds were shown to reduce blood glucose by suppression of glucagon secretion and stimulation of glucose-dependent insulin secretion. These antidiabetic agents have a minor risk of hypoglycemia and have been suggested as a second-line therapy to be added to metformin treatment to further optimize glycemic control in diabetes. More recently, scientific evidence suggests that GLP-1 receptor agonists may particularly afford protection from diabetic nephropathy through modulation of the molecular pathways involved in renal impairment and so improve renal function. This additional benefit adds further weight for these compounds to become promising drugs not only for glycemic control but also to prevent diabetic complications. In this review, we have updated evidence on the beneficial effects of GLP-1 receptor agonists on diabetic nephropathy and detailed the underlying pathophysiological mechanisms.