Insulin Signal Transduction Research Articles

Effect of electroacupuncture at different frequencies on brain insulin signaling transduction pathway in Alzheimer's disease mice

To observe the effect of electroacupuncture (EA) at different frequencies on learning and memory functions, as well as the relevant proteins of brain insulin signal transduction pathway in Alzheimer's disease (AD) mice and explore the effect mechanism of EA in treatment of AD. Seventy-two SPF Kunming male mice were randomized into a blank group, a sham-operation group, a model group, a 2 Hz EA group, a 15 Hz EA group and a 30 Hz EA group, 12 mice in each one. In the model group and each EA group, AD model were established by the injection with streptozotocin (ST2) solution (8 mg/kg) into the left lateral ventricles. In the sham-operation group, 0.9% sodium chloride solution of the same volume was injected into the left lateral ventricles. After successful modeling, in each EA group, EA was applied at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) with corresponding frequencies, once daily. One course of EA intervention consisted of 7 treatments and 2 courses were given totally at interval of 1 day. After modeling and intervention, Morris water maze test was conducted for the mice of each group. Using immunohistochemistry and Western blot method, the protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) was detected in the hippocampal of the mice after intervention. Compared with the blank group, in the model group, the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) after modeling. When compared with the blank group, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) in the model group after intervention. In the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all shortened (P<0.01), and the number of crossing the platform was increased (P<0.05, P<0.01) after intervention when compared with the model group. The escape latency and the first time of crossing the platform were all shortened (P<0.01, P<0.05), and the number of crossing the platform was increased (P<0.05) in the 15 Hz and 30 Hz EA groups in comparison with the 2 Hz EA group. The protein expression levels of IR, IRS-1 and PI3K were reduced in the model group when compared with those of the blank group (P<0.01, P<0.05); and these protein expression levels were increased in the 15 Hz and 30 Hz EA groups compared with the model group (P<0.05, P<0.01). Compared with the 2 Hz EA group, the protein expression levels of IR, IRS-1 and PI3K were all elevated in the 15 Hz and 30 Hz EA groups (P<0.05). The learning and memory function of AD mice may be improved through regulating brain insulin signaling transconduction pathway with electroacupuncture, and electroacupuncture at 15 Hz and 30 Hz obtains the overall better effect compared with the intervention at 2 Hz.

Liuwei Dihuang Pills in the Treatment of Senile Dementia: A Review

Objective To elucidate the synergistic mechanism of Liuwei Dihuang Pills (LWDHP), with multi-components, multi-targets and multi-channels in the treatment of senile dementia. Methods We searched Chinese and English databases to obtain the blood components of LWDHP, its clinical and preclinical mechanism research progress in the treatment of senile dementia. Based on the network pharmacology of the key pathophysiological process of Alzheimer’s disease (AD), we screened the anti-AD target of LWDHP and its blood components. Results The therapeutic effect of LWDHP on senile dementia is accurate, with few adverse reactions. Its mechanism includes regulation of cholinergic system, autophagy, cerebral microvascular function, neuron apoptosis, insulin signal transduction pathway, etc. In this review, 35 blood components of LWDHP based on HPLC were collected, and their drug toxicity and safety were evaluated. The network pharmacology analysis based on the pathophysiological process of AD shows that the key components of LWDHP in the treatment of AD are Alisol A monoacetate, Linoleic acid, Alisol F, Tumulosic acid, Methyl eugenol, Palmitic acid and Pachymic acid. Conclusion This article summarizes 35 blood components of LWDHP, summarizes the synergistic mechanism of LWDHP in the treatment of senile dementia, uses network pharmacology to provide a series of potential lead compounds for the development of senile dementia’s drugs, and provides a theoretical basis for further expanding the clinical application of LWDHP.

Phosphatidylserine in Diabetes Research.

Phospholipids are lipids that constitute the basic structure of cell membranes. In-depth research has shown that in addition to supporting cell structures, phospholipids participate in multiple cellular processes, including promoting cell signal transduction, guiding protein translocation, activating enzymatic activity, and eliminating dysfunctional/redundant organelles/cells. Diabetes is a chronic metabolic disease with a complicated etiology and pathology. Studies have shown that the level of certain phospholipids, for example, the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver tissue, is negatively associated with insulin sensitivity. In addition, PS is a phospholipid exhibiting extensive cellular functions in diabetes. For this review, we analyzed many PS studies focusing on diabetes and insulin sensitivity in recent years and found that PS participates in controlling insulin secretion, regulating insulin signaling transduction, and participating in the progression of diabetic complications by mediating coagulation disorders in the microvasculature or targeting mitochondria. Moreover, PS supplements in food and PS-containing liposomes have been shown to protect against type 1 and type 2 diabetes (T1D and T2D, respectively) in animal studies. Therefore, by summarizing the regulatory roles played by PS in diabetes and the potential of successfully using PS or PS-containing liposomes for diabetic therapy, we hope to provide new ideas for further research into the mechanisms of diabetes and for drug development for treating diabetes and its complications.

The role of pioglitazone in the fight against insulin resistance, atherosclerosis, cardiovascular disease, and non-alcoholic fatty liver disease

Modern strategies for the treatment of type 2 diabetes mellitus involve the use of pathogenetically based approaches aimed at achieving optimal glycemic control and its long-term retention. Timely and rational use of 9 classes of hypoglycemic drugs, including as part of combination therapy, makes it possible to achieve significant success in diabetes therapy. One of the fundamental principles in the treatment of type 2 diabetes mellitus is the effect on insulin resistance. For this purpose, two groups of drugs are used: biguanides and thiazolidinediones (glitazones). The action of glitazones is directly related to an increase in the sensitivity of insulin-dependent tissues to insulin and a pronounced decrease in hyperinsulinemia in patients with type 2 diabetes. Of particular interest are the pathways of insulin signal transduction, the mechanisms of insulin resistance, and the possibilities of pathogenetic therapy with thiazolidinediones. Pioglitazone is currently the only available member of the thiazolidinedione class in the world, allowing to expand the management of diabetes mellitus by reducing insulin resistance in muscle and adipose tissue and glucose production by the liver. Its use can have a number of pleiotropic effects, including on cardiovascular diseases and non-alcoholic fatty liver disease, which expands the priorities for choosing hypoglycemic therapy in patients with type 2 diabetes at various stages of therapy.

Genetic predisposition to gestational diabetes mellitus in the Kazakh population

Background and aimsThe purpose of the study was to conduct a comparative analysis of population frequencies of alleles and genotypes of polymorphic variants of genes for impaired insulin synthesis and associated with insulin signal transduction. MethodsThis investigation uses a genomic database of 1800 conditionally healthy individuals of Kazakh ethnicity, who underwent full genome genotyping using OmniChip 2.5–8 Illumina chips of ∼2.5 million Single Nucleotide Polymorphism at deCODE Iceland Genomic Centre. ResultsThe highest frequency of carriage of minor A allele – 17.6% rs4607517 polymorphism of Glucokinase gene, unfavorable genotypes A/G – 29.5% and A/A – 3.0% in comparison with European and Asian populations, indicates a contribution of hereditary family forms of Maturity-onset diabetes of the young type 2 to gestational diabetes mellitus in Kazakh population. ConclusionsThe study of the associations of genetic markers of gestational diabetes mellitus will allow timely identification of high-risk groups before and at an early stage of pregnancy, carrying out the necessary effective preventive measures and, in the case of gestational diabetes mellitus development, optimizing the correction of carbohydrate metabolism disorders and predicting outcomes for the mother and the fetus.

Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment.

This study explored the possible connection between the insulin resistance-targeting protein adipokine lipocalin-2 (LCN-2) and NF-κB signaling pathway in the inflammatory microenvironment in PCOS-IR model rats to determine the pharmacological mechanism of modified Cangfu Daotan decoction (MCDD) intervention for PCOS-IR. We used a high-fat diet (42 days) combined with letrozole (1 mg/kg/day, 42 days) to establish a PCOS-IR rat model. From the third week after modeling, the rats were given continuous administration of MCDD (high dose with 31.68 g/kg, medium dose with 15.84 g/kg, and low dose with 7.92 g/kg) for 28 days. Serum, ovarian tissue, liver, and adipose tissue were collected after the last gavage. Enzyme-linked immunosorbent assay, hematoxylin-eosin (HE) staining, Masson staining, qRT-PCR, and Western blot experiments were performed to detect various indicators. Our results showed that MCDD could reduce body weight and abdominal fat weight; restore normal estrous cycle and ovarian function; alleviate fatty liver; regulate HOMA-IR and OGTT index; reduce serum inflammatory factor levels, LCN-2 level, and gene expression; and regulate the insulin signal transduction and NF-κB pathways in PCOS-IR rats. Thus, MCDD may play a role in improving ovarian function in PCOS-IR rats by downregulating NF-κB/LCN-2 proteins and upregulating the gene expression of Insr/Irs-1/Glut4 in the insulin signaling pathway in the inflammatory environment.

The insulin signaling pathway a century after its discovery: Sexual dimorphism in insulin signaling

Since practically a century ago, the insulin pathway was discovered in both vertebrates and invertebrates, implying an evolutionarily ancient origin. After a century of research, it is now clear that the insulin signal transduction pathway is a critical, flexible and pleiotropic pathway, evolving into multiple anabolic functions besides glucose homeostasis. It regulates paramount aspects of organismal well-being like growth, longevity, intermediate metabolism, and reproduction. Part of this diversification has been attained by duplications and divergence of both ligands and receptors riding on a common general signal transduction system. One of the aspects that is strikingly different is its usage in reproduction, particularly in male versus female development and fertility within the same species. This review highlights sexual divergence in metabolism and reproductive tract differences, the occurrence of sexually “exaggerated” traits, and sex size differences that are due to the sexes’ differential activity/response to the insulin signaling pathway.

Ginsenoside F2 enhances glucose metabolism by modulating insulin signal transduction in human hepatocarcinoma cells

BackgroundGinsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. MethodsHepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. ResultsCell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. ConclusionOverall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

Sexual dimorphism in the molecular mechanisms of insulin resistance during a critical developmental window in Wistar rats

BackgroundInsulin resistance (IR) is a condition in which the response of organs to insulin is impaired. IR is an early marker of metabolic dysfunction. However, IR also appears in physiological contexts during critical developmental windows. The molecular mechanisms of physiological IR are largely unknown in both sexes. Sexual dimorphism in insulin sensitivity is observed since early stages of development. We propose that during periods of accelerated growth, such as around weaning, at postnatal day 20 (p20) in rats, the kinase S6K1 is overactivated and induces impairment of insulin signaling in its target organs. This work aimed to characterize IR at p20, determine its underlying mechanisms, and identify whether sexual dimorphism in physiological IR occurs during this stage.MethodsWe determined systemic insulin sensitivity through insulin tolerance tests, glucose tolerance tests, and blood glucose and insulin levels under fasting and fed conditions at p20 and adult male and female Wistar rats. Furthermore, we quantified levels of S6K1 phosphorylated at threonine 389 (T389) (active form) and its target IRS1 phosphorylated at serine 1101 (S1101) (inhibited form). In addition, we assessed insulin signal transduction by measuring levels of Akt phosphorylated at serine 473 (S473) (active form) in white adipose tissue and skeletal muscle through western blot. Finally, we determined the presence and function of GLUT4 in the plasma membrane by measuring the glucose uptake of adipocytes. Results were compared using two-way ANOVA (With age and sex as factors) and one-way ANOVA with post hoc Tukey’s tests or t-student test in each corresponding case. Statistical significance was considered for P values < 0.05.ResultsWe found that both male and female p20 rats have elevated levels of glucose and insulin, low systemic insulin sensitivity, and glucose intolerance. We identified sex- and tissue-related differences in the activation of insulin signaling proteins in p20 rats compared to adult rats.ConclusionsMale and female p20 rats present physiological insulin resistance with differences in the protein activation of insulin signaling. This suggests that S6K1 overactivation and the resulting IRS1 inhibition by phosphorylation at S1101 may modulate to insulin sensitivity in a sex- and tissue-specific manner.1x839z9cy-UAMHakhorVgrVideo

Effects of p-Hydroxybenzaldehyde, Vanillin, and Syringaldehyde on Protein Tyrosine Phosphatase 1B Activity

Background: The PTP 1B is a negative regulator of insulin signal transduction and hence, serves as a therapeutic target in the treatment of diabetes. Objective: The present study investigated the inhibitory effects of p-hydroxybenzaldehyde, vanillin, and syringaldehyde on the activity of protein tyrosine phosphatases phosphatase 1B (PTP 1B) in vitro. Method: The PTP 1B inhibitory assay and mode of inhibition of the three compounds were determined using p-nitrophenyl phosphate (p-NPP) in a 96 well microplate. Molecular docking was used to predict the binding affinities of the compounds with the PTP 1B. Results: The results showed that syringaldehyde exhibited significantly (p&lt; 0.05) higher PTP 1B inhibitory activity (IC50: 12.75 µM) compared to p-hydroxybenzaldehyde (IC50: 33.79 µM) and vanillin (IC50: 42.82 µM) as well as the standards suramin (IC50: 28.35 µM) and ursolic acid (IC50: 19.45 µM). Syringaldehyde and vanillin showed uncompetitive inhibition whereas, p-hydroxybenzaldehyde showed a mixed inhibition type. The molecular docking simulation predicted negative binding energies of -5.0 kcal/mol, -5.5 kcal/mol, and -5.5 kcal/mol for p-hydroxybenzaldehyde, vanillin, and syringaldehyde respectively. Conclusion: Syringaldehyde showed higher inhibition of PTP 1B compared to other phenolic aldehydes and could be the mechanism of its antidiabetic activity. Hence, further studies are warranted to confirm the efficacy and toxicity of the compound

Neuroendocrine microRNAs linked to energy homeostasis: future therapeutic potential.

The brain orchestrates whole-body metabolism through an intricate system involving interneuronal crosstalk and communication. Specifically, a key player in this complex circuitry is the hypothalamus that controls feeding behaviour, energy expenditure, body weight and metabolism, whereby hypothalamic neurons sense and respond to circulating hormones, nutrients, and chemicals. Dysregulation of these neurons contributes to the development of metabolic disorders, such as obesity and type 2 diabetes. The involvement of hypothalamic microRNAs, post-transcriptional regulators of gene expression, in the central regulation of energy homeostasis has become increasingly apparent, although not completely delineated. This review summarizes current evidence demonstrating the regulation of feeding-related neuropeptides by brain-derived microRNAs as well as the regulation of specific miRNAs by nutrients and other peripheral signals. Moreover, the involvement of microRNAs in the central nervous system control of insulin, leptin, and estrogen signal transduction is examined. Finally, the therapeutic and diagnostic potential of microRNAs for metabolic disorders will be discussed andthe regulation of brain-derived microRNAs by nutrients and other peripheral signals is considered. Demonstrating a critical role of microRNAs in hypothalamic regulation of energy homeostasis is an innovative route to uncover novel biomarkers and therapeutic candidates for metabolic disorders.

Effect of chitooligosaccharides with a specific degree of polymerization on multiple targets in T2DM mice

Chitooligosaccharides (COS) are found naturally in the ocean and present a variety of physiological activities, of which hypoglycemic action has attracted considerable research attention. This study aimed to assess the therapeutic effect of COS on mice suffering from type 2 diabetes mellitus (T2DM). COS effectively reduced blood glucose and blood lipid levels and improved glucose tolerance. Furthermore, COS revealed strong inhibitory activity against α-glucosidase, reducing postprandial blood glucose levels. Molecular docking data showed that COS might interact with surrounding amino acids to form a complex and decrease α-glucosidase activity. Additionally, COS enhanced insulin signal transduction and glycogen synthesis while restricting gluconeogenesis in the liver and muscles, reducing insulin resistance (IR) as a result. Moreover, COS effectively protected and restored islet cell function to increase insulin secretion. These results indicated that COS exhibited a significant hypoglycemic effect with multi-target participation. Therefore, COS may serve as a new preventive or therapeutic drug for diabetes to alleviate metabolic syndrome.Graphical

Lycopene attenuates oxidative stress-induced hepatic dysfunction of insulin signal transduction: involvement of FGF21 and mitochondria

Lycopene (LYC) has been regarded as a nutraceutical that has powerful antioxidant and hepatoprotective bioactivities. In the present study, we aimed to investigate the beneficial effects of LYC on hepatic insulin signal transduction under oxidative stress conditions and the possible involvement of FGF21 and mitochondria pathways. Two-month-old CD-1 mice were treated by intraperitoneal injection of D-galactose (D-gal) 150 mg/kg/day for 8 weeks and received 0.03% LYC (w/w, mixed into diet). The results showed that LYC increased the expression of FGF21, alleviated mitochondrial dysfunction and improved hepatic insulin signal transduction in D-gal-treated mice. Furthermore, knockdown of FGF21 by small interfering RNA notably suppressed mitochondrial function and blunted LYC-stimulated insulin signal transduction in H2O2-treated HepG2 cells. Moreover, suppressed mitochondrial function via oligomycin also inhibited insulin signal transduction, indicating that LYC supplementation ameliorated oxidative stress-induced hepatic dysfunction of insulin signal transduction by up-regulating FGF21 and enhancing mitochondrial function.

DLBS3233 reduces inflammatory marker on kidney by increasing expression GLUT1 and GLUT2 in diabetic rats

Introduction: Diabetic kidney disease (DKD), as a diabetes mellitus type 2 (DMT2) complications, is getting more prevalent nowadays. Inflammation is one of the renal injury mechanisms evaluated through the surge in in TNF-α and NF-κβ expression. Impaired expression of gluten transporter 1 (GLUT1) and GLUT2 reduces glucose uptake. DBLS3233 is a novel anti-diabetes agent and Indonesian herbal product responsible for glucose control and upregulation of insulin signal transduction. We performed an experiment on DLBS3233 to examine the response of TNF-α and NF-κβ and the expression of GLUT 1 and GLUT2. Methods: A total of 30 adult male Wistar rats were randomly divided into six groups (n=5 per group): nondiabetic rats in the control group (group 1); untreated diabetic rats (group 2); diabetic rats treated with DLBS3233 4,5mg/kgBW (group 3); 9mg/kgBW (group 4); 18mg/kgBW (group 5), and diabetic rats treated with pioglitazone (group 6). Immunohistochemistry was performed to examine the expression of GLUT1 and GLUT2 in the pancreas and expression of TNF-α and NF-κβ in the kidney. The data was then analyzed by ANOVA. Results: In the DBLS3233 group, reduced expression of both TNF-α and NF-κβ was seen through immunohistochemistry, whereas GLUT1 and GLUT2 were intensified compared to untreated groups. From statistical analysis, we obtained significantly lower expression of TNF-α and NF-κβ, as well as enhanced GLUT1 and GLUT2 expression compared to untreated groups (p&lt;0.05). Conclusions: DBLS3233 significantly reduces the inflammatory process and enhances the expression of GLUT1 and GLUT2 diabetic rats.

The role of autophagy in high-fat diet-induced insulin resistance of adipose tissues in mice.

AimsStudies have observed changes in autophagic flux in the adipose tissue of type 2 diabetes patients with obesity. However, the role of autophagy in obesity-induced insulin resistance is unclear. We propose to confirm the effect of a high-fat diet (HFD) on autophagy and insulin signaling transduction from adipose tissue to clarify whether altered autophagy-mediated HFD induces insulin resistance, and to elucidate the possible mechanisms in autophagy-regulated adipose insulin sensitivity.MethodsEight-week-old male C57BL/6 mice were fed with HFD to confirm the effect of HFD on autophagy and insulin signaling transduction from adipose tissue. Differentiated 3T3-L1 adipocytes were treated with 1.2 mM fatty acids (FAs) and 50 nM Bafilomycin A1 to determine the autophagic flux. 2.5 mg/kg body weight dose of Chloroquine (CQ) in PBS was locally injected into mouse epididymal adipose (10 and 24 h) and 40 µM of CQ to 3T3-L1 adipocytes for 24 h to evaluate the role of autophagy in insulin signaling transduction.ResultsThe HFD treatment resulted in a significant increase in SQSTM1/p62, Rubicon expression, and C/EBP homologous protein (CHOP) expression, yet the insulin capability to induce Akt (Ser473) and GSK3β (Ser9) phosphorylation were reduced. PHLPP1 and PTEN remain unchanged after CQ injection. In differentiated 3T3-L1 adipocytes treated with CQ, although the amount of phospho-Akt stimulated by insulin in the CQ-treated group was significantly lower, CHOP expressions and cleaved caspase-3 were increased and bafilomycin A1 induced less accumulation of LC3-II protein.ConclusionLong-term high-fat diet promotes insulin resistance, late-stage autophagy inhibition, ER stress, and apoptosis in adipose tissue. Autophagy suppression may not affect insulin signaling transduction via phosphatase expression but indirectly causes insulin resistance through ER stress or apoptosis.

Anti-diabetic effect of banana peel dietary fibers on type 2 diabetic mellitus mice induced by streptozotocin and high-sugar and high-fat diet.

We used a high-fat diet (HFD) and streptozotocin (STZ) to induce type 2 diabetic mellitus (T2DM) mice and evaluated the effect of banana peel dietary fibers (BP-DFs) as potential hypoglycemic agents. After 5 weeks of intervention with banana peel dietary fibers (BP-DFs), food intake was reduced, body weight was increased, blood lipids and glucose were reduced, fasting insulin and GLP-1 levels were increased, and liver and pancreatic tissue damage was reduced. Banana peel soluble dietary fiber (BP-SDF) has the most significant effect. The results of fecal microbiota analysis showed that BP-DFs could ameliorates gut microbiome dysbiosis, and all three types of dietary fibers have obvious effects. The results of fecal short-chain fatty acids (SCFAs) showed that the content of fecal SCFAs was increased after BP-DFs dietary intervention, and BP-SDF had the most obvious effect. RT-PCR experiment results show that BP-DFs can up-regulate the mRNA expression levels of PI3K, AKT, IRS-1, and FOXO1 in the liver of diabetic mice, which indicates that BD-DFs may play a role in improving insulin resistance and insulin signal transduction via the IRS/PI3K/AKT pathway, improving insulin resistance and insulin signal transduction. Our research may be extended to BP-DFs, especially BP-SDF, as the basis for potential dietary intervention to prevent or treat type 2 diabetic mellitus. This work supports future research studies of the anti-diabetic properties of BP-SDF in humans. PRACTICAL APPLICATIONS: Diabetes can lead to a variety of complications that have a huge impact on health. Dietary fiber may help in lowering blood sugar. Our experimental results showed that banana peel dietary fibers have the effect of reducing food intake, blood sugar, improving liver and pancreas function, increasing the abundance of intestinal flora, and improving the IRS/PI3K/AKT pathway in T2DM mice. Therefore, this study could provide a theoretical basis for the development of functional foods with banana peel dietary fiber.

Obesity is the biggest driver of metabolic diseases lets focus on our waists

Obesity is the main determining factor of whole body reduced insulin sensitivity. This association has been demonstrated in multiple adult and pediatric cohorts. A close-fitting relation exists between typical lipid depositions patterns, exactly within the skeletal muscle and liver, as well as the intra-abdominal compartment and whole body insulin sensitivity causing different metabolic disorders. The effect of lipid deposition within insulin responsive tissues such as the liver and skeletal muscle relates to the ability of fatty acid derivate to inhibit elements of the insulin signal transduction pathway. Firming the relation of obesity and reduced insulin sensitivity are the annotations that weight gain reduces insulin sensitivity while weight loss increases it. This displays as the appearance of cardiovascular risk factor clustering with weight gain and its recovery in the face of weight loss. Both obesityand low insulin sensitivity, are independent determinants of the adverse metabolic phenotype characteristic of the metabolic syndrome.

Significance of Brain Glucose Hypometabolism, Altered Insulin Signal Transduction, and Insulin Resistance in Several Neurological Diseases.

Several neurological diseases share pathological alterations, even though they differ in their etiology. Neuroinflammation, altered brain glucose metabolism, oxidative stress, mitochondrial dysfunction and amyloidosis are biological events found in those neurological disorders. Altered insulin-mediated signaling and brain glucose hypometabolism are characteristic signs observed in the brains of patients with certain neurological diseases, but also others such as type 2 diabetes mellitus and vascular diseases. Thus, significant reductions in insulin receptor autophosphorylation and Akt kinase activity, and increased GSK-3 activity and insulin resistance, have been reported in these neurological diseases as contributing to the decline in cognitive function. Supporting this relationship is the fact that nasal and hippocampal insulin administration has been found to improve cognitive function. Additionally, brain glucose hypometabolism precedes the unmistakable clinical manifestations of some of these diseases by years, which may become a useful early biomarker. Deficiencies in the major pathways of oxidative energy metabolism have been reported in patients with several of these neurological diseases, which supports the hypothesis of their metabolic background. This review remarks on the significance of insulin and brain glucose metabolism alterations as keystone common pathogenic substrates for certain neurological diseases, highlighting new potential targets.

Marsupsin Isolated from Polyherbal Product ABPA Rejuvenates Insulin Resistance in L6 Skeletal Muscle Cell Line via IRS1‐PI3K‐AKT‐GLUT4 Signaling Pathway

BackgroundInsulin resistance (IR) is one of the key characteristics of type 2 diabetes mellitus (T2DM) which impairs the insulin signal transduction pathway. It is typically caused by many factors including hyperglycemia, accumulation of advanced glycation end products (AGEs), chronic oxidative stress and hyperlipidemia. Hence, complementary medicine such as herbal medications have been widely used as a complement to allopathic medicine to facilitate its efficacy while minimizing its potential adverse effects. ABPA is a polyherbal formulation that consists several powerful antidiabetic agents such as Pterocarpus marsupium. Our previous study showed that ABPA exhibited strong antidiabetic effect and detected high expression of marsupsin through HPLC studies.ObjectiveThe current study aims to elucidate the effect of marsupsin in rejuvenating insulin resistance through the IRS1‐PI3K‐AKT‐GLUT4 insulin signaling pathway.MethodL6 skeletal muscle cells were cultured and differentiated into L6 myotubes under standard conditions. The differentiated L6 myotubes were induced with high insulin to mimic insulin resistance and treated. Glucose uptake assay was also conducted to evaluate the effect of marsupsin on the rate of glucose uptake in the L6 cells. The cells were then lysed to extract the protein and RNA where the protein and differential gene expression of IRS1, PI3K, AKT and GLUT4 were analyzed using ELISA, qPCR, and Western Blot respectively.ResultsThe rate of glucose uptake was higher in MAR‐treated cells as compared to the negative control. This was further confirmed in the ELISA, qPCR and Western Blot analysis where MAR‐treated cells showed an upregulation of IRS1, PI3K, AKT and GLUT4 proteins as compared to the vehicle control.ConclusionMarsupsin rejuvenates insulin resistance in skeletal muscle cells by increasing the rate of glucose uptake through the activation of the IRS1‐PI3K‐AKT‐GLUT4 pathway.

Effects of Statin Drugs on New Onset of Diabetes Mellitus in Post Menopausal Women

Background: Statin drugs are using all over the world for the treatment of hypercholesterolemia. There is hypothesis that post menopausal women who used statin drugs long time can develop the onset of type 2 diabetes mellitus because statin drugs inhibit the signal transduction of insulin by inhibiting oxidative phosphorylation resulting in decrease secretion of insulin leads to hyperglycemia. The aim of this study to estimate the effects of statin drugs on blood glucose level and HbA!c% in post menopausal women.&#x0D; Methodology: This case comparative study was done at LUMHS Jamshoro. The sampling was done by Non Probability method. Total number of150 subjects were divided in 2 group’s i.e group A (Control group) &amp; group B (Case study group). The fasting glucose level was measured by glucose oxidase method while HbA1c% &amp; serum cholesterol levels were determined by Kit method by using auto analyzer. The statistical analysis was done by SPSS 21 by applying ANOVA test for multiple variants. &#x0D; Results: The mean with S.D fasting blood glucose levels in control group was 78± 9.05 mg/dl while in case study group it was 134 ± 12.15mg/dl (p &lt;0.05), HbA1c% levels in control group was 5.3 ± 1.1% while in case study group it was 7.4 ± 1.3% (p&lt;0.05) and serum cholesterol in control group was 157± 9.75 mg/dl while in case study group it was 195 ± 8.78 mg/dl (p&lt;0.05) was significantly (P&lt;0.05). The glycemic index &amp; fasting blood glucose levels significantly observed elevated in post menopausal women who were use statin drugs since last three years&#x0D; Conclusion: This study concluded that there was significant relation of statin drugs on increasing of blood glucose levels so they can induce the onset of Type-2 Diabetes Mellitus.