Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it’s role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer’s disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Anti-hyperglycemic and anti-hyperlipidemic effects of a methanolic extract of Debregeasia salicifolia in Alloxan-induced diabetic albino mice

Diabetes mellitus (DM), an endocrine syndrome characterized by high blood glucose levels due to abrogated insulin activity. The existing treatments for DM have side effects and varying degrees of efficacy. Therefore, it is paramount that novel approaches be developed to enhance the management of DM. Therapeutic plants have been accredited as having comparatively high efficacy with fewer adverse effects. The current study aims to elucidate the phytochemical profile, anti-hyperlipidemic, and anti-diabetic effects of methanolic extract D. salicifolia (leaves) in Alloxan-induced diabetic mice. Alloxan was injected intraperitoneally (150 mg kg-1, b.w), to induced diabetes in mice. The mice were divided into three groups (n=10). Group 1 (normal control) received normal food and purified water, Group II (diabetic control) received regular feed and clean water and group III (diabetic treated) received a methanolic extract of the plant (300 mg kg-1) for 28 days with a typical diet and clean water throughout the experiment. Blood samples were collected to checked serum glucose and concentration of LDL, TC, TG. The extract demonstrated significant antihyperglycemic activity (P<0.05), whereas improvements in mice's body weight and lipid profiles were observed after treatment with the extract. This study establishes that the extract has high efficacy with comparatively less toxicity that can be used for DM management.

Preventive Efficacy of an Antioxidant Compound on Blood Retinal Barrier Breakdown and Visual Dysfunction in Streptozotocin-Induced Diabetic Rats

In diabetic retinopathy (DR), high blood glucose drives chronic oxidative stress and inflammation that trigger alterations of the neurovascular balance finally resulting in vascular abnormalities and retinal cell death, which converge towards altered electroretinogram (ERG). In the last years, a growing body of preclinical evidence has suggested that nutrients with anti-inflammatory/antioxidant properties can be able to hamper DR progression since its very early stages. In the present study, we used a streptozotocin-induced rat model of DR, which mimics most aspects of the early stages of human DR, to test the preventive efficacy of a novel compound containing cyanidin-3-glucoside (C3G), verbascoside and zinc as nutrients with antioxidant and anti-inflammatory properties. Western blot, immunofluorescence and electroretinographic analyses demonstrated a dose-dependent inhibition of oxidative stress- and inflammation-related mechanisms, with a significant counterpart in preventing molecular mechanisms leading to DR-associated vasculopathy and its related retinal damage. Preventive efficacy of the compound on dysfunctional a- and b-waves was also demonstrated by electroretinography. The present demonstration that natural compounds, possibly as a consequence of vascular rescue following ameliorated oxidative stress and inflammation, may prevent the apoptotic cascade leading to ERG dysfunction, adds further relevance to the potential application of antioxidants as a preventive therapy to counteract DR progression.

Potentially synergistic effects of melatonin and metformin in alleviating hyperglycaemia: a comprehensive review

High level of glucose is hazardous for organisms since it leads to lipid peroxidation, protein glycation and free radical generation. Insulin can lower the high blood glucose by promoting cell’s glucose up-taking. Thus, the impeded insulin secretion in type 1-diabetes and insensitivity of cells to insulin in type 2-diabetes cause hyperglycaemia. Hyperglycaemia impairs mitochondrial function of pancreas to trigger ROS generation. The malfunctional mitochondria cause endoplasmic reticulum to produce misfolded non-functional insulin, finally leading to diabetes. Melatonin, the mitochondria targeted antioxidant, provides protection against diabetes by multiple ways. These include balancing cellular redox status, lowering blood glucose level by modulating metabolic pathways and, finally protecting cells/organelles from high glucose induced injury. Moreover, this indoleamine preserves pancreatic physiological normalcy to facilitate insulin secretion. Thus, melatonin can effectively mitigate diabetes and diabetic complications. Metformin, the most prescribed medicine for type 2-diabetes, has similar antidiabetic activities as melatonin. Both the molecules share similar pathways to preserve stress-stricken pancreas and other organs, whereas, melatonin also potentiates the actions of metformin. The potentially synergistic actions of melatonin and metformin are expected and we strongly recommend a combined therapeutic application of these two molecules for treatment of diabetes.

THE RELATIONSHIP BETWEEN SELF-MANAGEMENT AND QUALITY OF LIFE AMONG PATIENTS WITH TYPE 2 DIABETES MELLITUS

Background: Diabetes Mellitus (DM) is a metabolic disease characterized by high blood glucose levels as a result of insufficient insulin secretion, impaired insulin activity or both. Patients with diabetes mellitus are at risk for complications that can affect their quality of life. These complications can be minimized through self-management. Objectives: The aim of this study was to determine the relationship between self-management and quality of life in type 2 DM patients. Design: This study was a quantitative research. The design in this study was a cross-sectional analytic with a sample of 75 people who were carried out at the endocrine polyclinic RS Pusat TNI Angkatan Laut (RSPAL) DR. Ramelan Surabaya. Research instrument used the Diabetes Self-Management Questionnaire (DSMQ) developed by Schmitt et al (2013) to determine the self-management of type 2 DM patients and to measure the quality of life using the Diabetes Quality of Life Brief (DQoL Brief) instrument developed by Burrough et al (2008). The sample siza with simple random sampling method, and data analysis using spearman rank test. Results: The results showed that there was a significant relationship between self-management and quality of life in type 2 DM patients (p-value = .000, r = .394). Conclusion: There is a significant positive relationship between the level of self-management and quality of life in type 2 DM patients. From the results of the Spearman test correlation coefficient, there is a positive sign. This means that the higher the patient's self-management, it will also improve the quality of their life. The implication of this study are nurses can increase patient knowledge by providing education that focuses on improving self-management and facilitating the provision of family support as well as supervision and monitoring related to self-management by type 2 DM patients.

Comparison of the Efficiency of Lepidium sativum, Ficus carica, and Punica granatum Methanolic Extracts in Relieving Hyperglycemia and Hyperlipidemia of Streptozotocin-Induced Diabetic Rats

Background. Diabetes mellitus (DM) is a metabolic disorder characterized by high blood glucose levels that occurs either due to insufficient insulin production or mounting resistance to its action. The purpose of this study was to investigate if methanolic extracts of Lepidium sativum seeds, Ficus carica, and Punica granatum leaves had any effect on blood sugar levels in normal and streptozotocin (STZ) diabetic rats, as well as to explore the most effective extract. Method. Healthy male albino rats weighing 185-266 g were divided into nine groups of eight rats each: normal control, diabetic control, diabetic rats with dietary supplements of L. sativum, F. carica, and P. granatum methanolic extracts, and diabetics treated with insulin. All of the rats were fed on ordinary diet with nutritional pellets and were given water ad libitum. To induce diabetes, all animals were administered with STZ intraperitoneal injection at a dose of 60 mg/kg body weight. For five weeks, the crude plant extracts were given orally to various groups of rats at doses of one hundred and two hundred mg/kg body weight. After that, animal groups were sacrificed and blood samples were taken. Results. Phytochemical analysis revealed that the highest amounts of polyphenolic compounds were present in L. sativum seeds and P. granatum leaves, while leaves of F. carica showed the highest amounts of alkaloid and flavonoid content compared to other extracts. Oral administration of F. carica and L. sativum extracts at the dosage of 100 and 200 mg/kg significantly reduced glucose, lipid profile, kidney, and liver enzyme levels. A significant increase in HbAlc levels was also observed with L. sativum extract at a dose of 200 mg/kg compared to diabetic controls. Mellitus rats supplemented with 100 and 200 mg/kg methanolic extracts of P. granatum had higher serum triglycerides and lower serum low-density lipoprotein cholesterol (LDL-C) than normal control rats. F. carica extract is more effective than L. sativum and P. granatum extracts in the prevention and control of type 2 diabetes mellitus (T2DM) and its consequences.

A Brief Review on Management of Gestational Diabetes

Gestational diabetes mellitus (GDM) is a real pregnancy trap, wherein ladies without as of late dissected diabetes encourage constant high blood glucose during pregnancy. Diabetes in gestation is a condition where highly increase in the blood glucose level at the period of pregnancy and impacts pregnant ladies who haven't been broke down with diabetes. Diabetes mellitus in gestational period is conceivably most broadly perceived serious the pregnant conditions, with long and short stretch outcomes for mothers, hatchlings & babies. The chiefs & remedies which are wanted to gain most ideal control of glycemia, and while ignoring hypoglycaemia & make sure of fetal and maternal prosperity. This incorporates direct changes, food & treatment, and when considered fundamental; For possible opposing outcomes, simultaneously with fetal and maternal perception was made. The response intends to develop choices for gestational diabetes management treatment pharmacologically. Everyone played out a wide composing different review of examinations, conveyed in the latest fifty year , focusing on treatment for Gestational diabetes mellitus pharmacologically, overseeing security & ampleness, for maternal & fetal unpleasantness results; similarly like disillusionment & accomplishment in developing legitimate control of glucose and metabolic conditions . Medical treatment orally is a secured & convincing treatment system for GDM and in specific conditions may fill in as first-line treatment while supporting changes misfire. Right when oral experts disregard to set up control of glucose then imbuements of insulin are added supposedly. Choosing oral treatment which is the best in unsure, disregarding the way that it seems, by all accounts, to be that metformin is fairly better compared to glyburide, in specific perspectives. Concerning parenteral treatment, all recorded insulins in the specified article need to be considered both ensured & practical so that the treatment of high blood glucose can be treated in pregnancy. Fundamentally, a prevalent security profile, with near feasibility is recorded for most analogs. As GDM normality climbs, there is a prerequisite for powerful noticing and treatment for patients.

Network Analysis Reveals Dysregulated Functional Patterns in Type II Diabetic Skin

Skin disorders are one of the most common complications of type II diabetes (T2DM). Long-term effects of high blood glucose leave individuals with T2DM more susceptible to cutaneous diseases, but its underlying molecular mechanisms are unclear. Network-based methods consider the complex interactions between genes which can complement the analysis of single genes in previous research. Here, we use network analysis and topological properties to systematically investigate dysregulated gene co-expression patterns in type II diabetic skin with skin samples from the Genotype-Tissue Expression database. Our final network consisted of 8,812 genes from 73 subjects with T2DM and 147 non-T2DM subjects matched for age, sex, and race. Two gene modules significantly related to T2DM were functionally enriched in the pathway lipid metabolism, activated by PPARA and SREBF (SREBP). Transcription factors KLF10, KLF4, SP1, and microRNA-21 were predicted to be important regulators of gene expression in these modules. Intramodular analysis and betweenness centrality identified NCOA6 as the hub gene while KHSRP and SIN3B are key coordinators that influence molecular activities differently between T2DM and non-T2DM populations. We built a TF-miRNA-mRNA regulatory network to reveal the novel mechanism (miR-21-PPARA-NCOA6) of dysregulated keratinocyte proliferation, differentiation, and migration in diabetic skin, which may provide new insights into the susceptibility of skin disorders in T2DM patients. Hub genes and key coordinators may serve as therapeutic targets to improve diabetic skincare.

Association of Quantified Costal Cartilage Calcification and Long-Term Cumulative Blood Glucose Exposure: The Multi-Ethnic Study of Atherosclerosis

AimsAnecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA).MethodsThe volume of bilateral CCC was quantified in high-density pixels (threshold of Hounsfield Unit&gt;180) using the CAC scoring CT images acquired in the 5th MESA exam. Prior long-term cumulative exposure to FBG was calculated by area under the FBG-time curve over ten years before the time of the CT exam.ResultsA total of 2,305 participants (mean age: 69, female/male: 1.3) were included in this study. The median CCC volume was lower in females than males (1158 mm3 [IQR: 1751] vs. 3054 mm3 [3851], p&lt;0.001). In cross-sectional analysis, quantified CCC was associated with FBG (9% increase per SD) and HbA1c (7% increase per SD) at the CT exam only in female participants after adjustment for age, race, BMI, and glomerular filtration rate. Only in female participants, quantified CCC was also associated with prior cumulative FBG (3% increase per decile change). In the subgroup of females with zero CAC scores, the adjusted CCC was still associated with FBG (13% increase per SD) at the time of CT exam and with prior cumulative FBG exposure (4% increase per decile change) before the CT exam.ConclusionsThe CCC, a reliably quantified marker in non-contrast cardiac CT, is associated with 10-year cumulative FBG exposure only in female participants, even those with zero CAC.

Hypoglycemic Effects of Plant Flavonoids: A Review

Diabetes mellitus is a metabolic disorder with chronic high blood glucose levels, and it is associated with defects in insulin secretion, insulin resistance, or both. It is also a major public issue, affecting the world's population. This disease contributes to long-term health complications such as dysfunction and failure of multiple organs, including nerves, heart, blood vessels, kidneys, and eyes. Flavonoids are phenolic compounds found in nature and usually present as secondary metabolites in plants, vegetables, and fungi. Flavonoids possess many health benefits such as anti-inflammatory and antioxidant activities, and naturally occurring flavonoids contribute to antidiabetic effects.Many studies conducted in vivo and in vitro have proven the hypoglycemic effect of plant flavonoids. A large number of studies showed that flavonoids hold positive results in controlling the blood glucose level in streptozotocin (STZ)-induced diabetic rats and further prevent the complications of diabetes. The future development of flavonoid-based drugs is believed to provide significant effects on diabetes mellitus and diabetes complication diseases. This review aims at summarizing the various types of flavonoids that function as hyperglycemia regulators such as inhibitors of α-glucosidase and glucose cotransporters in the body. This review article discusses the hypoglycemic effects of selected plant flavonoids namely quercetin, kaempferol, rutin, naringenin, fisetin, and morin. Four search engines, PubMed, Google Scholar, Scopus, and SciFinder, are used to collect the data.