Decreased Insulin Resistance Research Articles

Metabolomics study on liver of db/db mice treated with curcumin using UPLC-Q-TOF-MS

A metabolomics method based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to study the metabolic changes of liver in db/db mice administered with curcumin. After one week of acclimating to feeding, 20 db/db mice were randomly divided into two groups: curcumin non-treatment group and curcumin treatment group. After eight weeks of treatment, plasma and liver were collected for biochemical analysis and metabolomics analysis, as well as liver oxidative stress and histopathology examination. Serum biochemical indicators such as blood glucose, triglycerides, fasting insulin, and aspartate aminotransferase decreased significantly in the curcumin treatment group compared to the curcumin non-treatment group, whereas hepatic pathological levels and antioxidation levels improved. There were several different potential biomarkers in two groups, including sphingomyelin (SM) (d18:0/20:0), eicosapentaenoic acid (EPA), docosapentaenoic acid (22n-6) (DPAn-6), arachidonic acid (AA), dihomo-gamma- linolenic acid (DGLA), leukotriene C4 (LTC4), lysophosphatidylethanolamine (LysoPE) (16:1(9Z)/0:0), LysoPE (18:1(9Z)/0:0), LysoPE (0:0/18:0), LysoPE (0:0/20:1(11Z)), LysoPE (20:1(11Z)/0:0), 3-sulfinoalanine, alpha-tocotrienol (α-T3) and pantetheine 4′-phosphate (4′-PP). The mechanism might be related to biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, phospholipid metabolism, and taurine and hypotaurine metabolism. The effects of curcumin on type 2 diabetes mellitus (T2DM) include antioxidant, delaying development of T2DM, preventing β-cell death, decreasing insulin resistance, alleviating hepatic damage, and improving metabolic disturbances. Our results provide novel insights and ideas for prevention and treatment of curcumin on T2DM and its complications.

Non-Alcoholic Fatty Liver Disease and the Risk of Diabetes Mellitus by Menopausal Status: A Nationwide Cohort Study.

Background: Non-alcoholic fatty liver disease (NAFLD) is regarded as a risk factor for type 2 diabetes mellitus (DM). Menopausal status also influences T2DM risk, where estrogen is presumed to play a protective role by decreasing insulin resistance. As such, we investigated the association between NAFLD and DM risk according to menopausal status. Objectives: We sought to examine the association between NAFLD and DM incidence in pre- and post-menopausal women. Methods: A total of 842,772 pre-menopausal and 1,074,767 post-menopausal women who underwent health examinations between 2009 and 2014 were included from the Korean National Health Insurance Service database. Multivariate Cox proportional hazard analyses were performed to evaluate the association between the risk of DM according to menopausal status and NAFLD, defined by a fatty liver index >60. Results: During the mean follow-up period (7.8 years), DM was diagnosed in 33,461 (4.0%) of pre-menopausal women and 121,102 (9.4%) post-menopausal women. A stronger association between NAFLD and the risk of DM was found in pre-menopausal women (multivariable-adjusted hazard ratio [aHR], 3.60; 95% confidence interval [CI], 3.48–3.71) than in post-menopausal women (aHR, 2.24; 95% CI, 2.21–2.28) (P-interaction < 0.01). Subgroup analyses among women aged 45 to 55 years also showed a stronger association in pre-menopausal (aHR, 3.35; 95% CI, 3.21–3.49) than in post-menopausal women (aHR, 2.83; 95% CI, 2.68–2.98) (P-interaction < 0.01). Conclusions: The association between NAFLD and DM was stronger in pre-menopausal women than in post-menopausal women. This might be due to the protective effect of estrogen, which is possibly in higher production in the peripheral fat tissue of post-menopausal women with NAFLD.

Improved Insulin Resistance and Glucose Variability by Super-Low Carbohydrate Diet

Background Diabetes mellitus (DM) has been more prevalent. American Diabetes Association (ADA) proposed the Standards of Medical Care in Diabetes-2022. For nutritional therapy, low carbohydrate diet (LCD) has been recognized for its benefits. Authors have continued diabetic research concerning LCD and meal tolerance test (MTT). Case Presentation The case is 61-year-old male with type 2 diabetes mellitus (T2DM) for years. His hemoglobin A1c (HbA1c) increased to 7.8% in autumn 2021, and further evaluation and treatment was conducted including LCD, daily check of meal and carbohydrate amount, 75 g OGTT, glucagon stimulation test (GST) and others. Results He was on super-LCD method including 12% of carbohydrate. His carbohydrate intake amount and 45-minutes post-prandial blood glucose showed significant correlation. The results of 75 g OGTT twice in May 2020 and December 2021 showed that similar pattern of glucose and insulin responses and insulinogenic index (IGI). In contrast, they showed decreased fasting immuno-reactive insulin (IRI) and Homeostasis model assessment insulin resistance (HOMA-R). For GST, C-peptide showed normal response. Discussion and Conclusion Judging from the results of MTT, OGTT, GST and IGI, he seems to show rather decreased insulin resistance by LCD associated with preserved insulin secretion ability to some degree. Further investigation would be required from pathophysiological point of view.

Effects of high intensity interval training on sustained reduction in cardiometabolic risk associated with overweight/obesity: A randomized trial

Background/ObjectivesConsidering the potential greater cardiocirculatory effects of high intensity interval training (HIIT), we hypothesized that a 2-month supervised high volume short interval HIIT would induce greater improvements in CRF and cardiometabolic risk and increase long-term maintenance to physical activity compared to isocaloric moderate intensity continuous training (MICT) in overweight/obesity. MethodsSixty (19 females) subjects with overweight/obesity were randomized to three training programs (3 times/week for 2 months): MICT (45 min, 50% peak power output-PPO), HIIT (22 × 1-min cycling at 100% PPO/1-min passive recovery) and HIIT-RM (RM: recovery modulation, i.e. subjects adjusted passive recovery duration between 30s and 2 min). After the intervention, participants no longer benefited from supervised physical activity and were instructed to maintain the same exercise modalities on their own. We assessed anthropometrics, body composition, CRF, fat oxidation, lipid profile, glycemic balance, low-grade inflammation, vascular function, spontaneous physical activity and motivation for eating at three time points: baseline (T0), 4 days after the end of the 2-month supervised training program (T2) and 4 months after the end of the training program (T6). ResultsHIIT/HIIT-RM induced greater improvement in VO2peak (between +14% and +17%), power output at ventilatory thresholds and at maximal fat oxidation rate (+25%) and waist circumference (−1.53 cm) compared to MICT and tended to decrease insulin resistance. During the four-month follow-up period during which exercise in autonomy was prescribed, HIIT induced a greater preservation of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL. ConclusionWe have shown greater short-term benefits induced by a high volume short interval (1 min) HIIT on cardiorespiratory fitness and cardiometabolic risk over an isocaloric moderate intensity continuous exercise in persons with overweight/obesity. We also showed greater long-term effects (i.e. after 4 months) of this exercise modality on the maintenance of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL.

Clinical Efficacy of Imeglimin (Twymeeg) for Elderly Patient with Type 2 Diabetes Mellitus (T2DM)

Background: As an oral hypoglycaemic agent (OHA), imeglimin (Twymeeg) has been recently introduced to clinical practice for patients with type 2 diabetes mellitus (T2DM) as Twymeeg. It has beneficial pharmacological mechanisms, which are improving insulin secretion, increasing insulin sensitivity, and decreasing insulin resistance. Case Presentation: The case is 84-year-old man with mild cognitive impairment (MCI) for 3 years. He visited late August, 2021 our clinic for general malaise and was pointed out to have post-prandial blood glucose 336 mg/dL and HbA1c 8.6%. He was diagnosed with T2DM. Results: He was started to be given imeglimin 1000mg twice a day, and then HbA1c value was decreased to 7.3% in 4 weeks and 5.7% in 8 weeks. During 9-12 weeks, he felt loss of appetite and reduced food intake. Biochemical examination on 12 weeks showed decreased values of TP, Alb, HbA1c, glucose, free T3, and normal values of TSH, free T4. Doses of imeglimin were 500 mg twice a day for 9-12 weeks and discontinued after 12 weeks. Discussion: Regarding appetite loss, possible causes may include MCI, previous history of gallbladder dyskinesia, adverse effect of imeglimin, and so on. Further development of research will be expected for imeglimin in the future.

Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease.

In recent years, the health of patients exposed to the consequences of the metabolic syndrome still requires the search for new solutions, and plant nutraceuticals are currently being intensively investigated. Berberine is a plant alkaloid possessing scientifically determined mechanisms of the prevention of the development of atherosclerosis, type 2 diabetes, and obesity, as well as cardiovascular complications and cancer. It positively contributes to elevated levels of fasting, postprandial blood glucose, and glycosylated hemoglobin, while decreasing insulin resistance. It stimulates glycolysis, improving insulin secretion, and inhibits gluconeogenesis and adipogenesis in the liver; by reducing insulin resistance, berberine also improves ovulation. The anti-obesity action of berberine has been also well-documented. Berberine acts as an anti-sclerotic, lowering the LDL and testosterone levels. The alkaloid exhibits an anti-inflammatory property by stalling the expression of cyclooxygenase 2 (COX-2) and prostaglandin E2. Berberine is neuroprotective and acts as an antidepressive. However, the outcomes in psychiatric patients are nonspecific, as it has been shown that berberine improves metabolic parameters in schizophrenic patients, acting as an adjuvant during antipsychotic treatment. Berberine acts as an anticancer option by inducing apoptosis, the cell cycle arrest, influencing MAPK (mitogen-activated protein kinase), and influencing transcription regulation. The inhibition of carcinogenesis is also combined with lipid metabolism.

Dietary Succinoglycan Riclin Improves Glycemia Control in Mice with Type 2 Diabetes.

Riclin is a typical succinoglycan produced by an agrobacterium isolate. Our previous investigation has revealed that oral riclin restores the islet function in type 1 diabetic mice. However, whether dietary riclin improves glycemic control in type 2 diabetes (T2D) is unknown. Here, we found that dietary riclin (20 and 40 mg/kg) for 4 weeks significantly decreased fasting blood glucose (55 and 67%), improved insulin sensitivity, and decreased insulin resistance in high-fat-diet/streptozocin (HFD/STZ)-induced T2D. Riclin reduced the proportion of T helper 1 cell subsets in diabetic mice, alleviated pancreatic inflammation, and protected islet function. Moreover, dietary riclin enriched the diversity of gut microflora and restored the relative abundance of several bacterial genera in diabetes, including the strains of Clostridium, Parasutterella, Klebsiella, and Bacteroides. In db/db diabetic mice, riclin also improves glycemia control as observed in HFD/STZ-induced T2D mice. These data suggest that riclin has potential to be a functional food to treat T2D.

Anti‐diabetic and gut microbiota modulation effects of sacha inchi (Plukenetia volubilis L.) leaf extract in streptozotocin‐induced type 1 diabetic mice

Sacha inchi (Plukenetia volubilis L.) tea has been used as an adjuvant treatment for diabetes in Pu'er, in the Yunnan province of China. The effects of sacha inchi tea on diabetes and the underlying mechanisms remain unknown. This study was conducted to investigate the influence of a water extract of sacha inchi (P. volubilis L.) leaves (PWE) on hypoglycemic activity and gut microbiota composition in mice with streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM). During the 6 weeks of the study, T1DM mice were administered PWE intragastrically at 400 mg kg-1 body weight (BW) per day. Treatment with PWE reduced excessive loss of BW and excessive intake of food. It significantly decreased blood glucose levels and improved oral glucose tolerance. The treatment caused protective histopathological transformations in sections of the pancreas, leading to decreased insulin resistance and improved insulin sensitivity. Treatment with PWE also significantly ameliorated disorders of the gut microbiota structure and increased the richness and diversity of intestinal microbial species in T1DM mice. At the genus level, the populations of several crucial bacteria, such as Akkermansia, Parabacteroides, and Muribaculum increased in the PWE treatment group but the abundance of Ruminiclostridium and Oscillibacter decreased. Treatment with PWE can ameliorate hyperglycemic symptoms in STZ-induced T1DM mice, and the anti-diabetic effect of PWE was related to the amelioration of gut microbial structural disorder and the enrichment of functional bacteria. © 2022 Society of Chemical Industry.

Evidence from a Systematic Review and Meta-Analysis Pointing to the Antidiabetic Effect of Polyphenol-Rich Plant Extracts from Gymnema montanum, Momordica charantia and Moringa oleifera.

In vitro and animal model studies are of great interest for selecting new phytochemicals, including polyphenols with antioxidative properties, as candidates for antidiabetic drugs. This review provides evidence from a critical literature data analysis on the effects of plant extract supplementation in diabetes mellitus management. We considered and meta-analyzed the efficacy of oral supplementation of plant extracts in animal model studies and examined physiological and oxidative stress parameters. Finally, 23 articles were included in the meta-analysis, revealing three plants with experimentally confirmed in vivo and in vitro antidiabetic properties: Gymnema montanum, Momordica charantia and Moringa oleifera. The following parameter changes resulted from an investigation of the supplementation: reduced oxidative stress, decreased insulin resistance, increased insulin release, reduced adiposity, and a modulatory effect on glycolysis and gluconeogenesis, as well as attenuation of diabetes-associated weight loss, reduced fasting blood glucose and lowered oxidative status. A comparison of Gymnema montanum versus Glybenclamide revealed the superiority of extracts over drug administration in some aspects. Although the analyzed extracts are promising candidates for antidiabetic treatment, there is much inconsistent data in the literature. Therefore, ultimate references for using these compounds in the prevention of diabetes are currently not applicable.

TLR13 contributes to skeletal muscle atrophy by increasing insulin resistance in chronic kidney disease.

ObjectivesInsulin resistance in chronic kidney disease (CKD) stimulates muscle wasting, but the molecular processes behind the resistance are undetermined. However, inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia. Toll‐like receptors (TLRs) are known to regulate local innate immune responses, and microarray data have shown that Tlr13 is upregulated in the muscles of mice with CKD, but the relevance is unknown.Materials and MethodsWe performed in vitro experiments in C2C12 myotubes and constructed a CKD murine model using subtotal nephrectomy to conduct experiments in vivo.Results Tlr13 expression was stimulated in C2C12 myotubes treated with uremic serum. The expression of Tlr13 was also upregulated in the tibialis anterior muscles of mice with CKD. Tlr13 knockdown with siRNAs in skeletal muscle cells decreased insulin resistance despite the inclusion of uremic serum. This led to increased levels of p‐AKT and suppression of protein degradation. Using immunofluorescence staining and coimmunoprecipitation assay, we found that TLR13 recruits IRF3, which activates Irf3 expression, resulting in decreased AKT activity. Moreover, insulin resistance and proteolysis are re‐induced by Irf3 overexpression under Tlr13 deletion.ConclusionsOur results indicate that TLR13 is involved in CKD‐mediated insulin resistance in muscle. In catabolic conditions where insulin signaling is impaired, targeting TLR13 may improve insulin sensitivity and prevent muscle atrophy.

An update on mode of action of metformin in modulation of meta-inflammation and inflammaging

Type 2 diabetes mellitus (T2DM) is the most common chronic metabolic condition. Several genetic and environmental factors are involved in developing T2DM. Aging, inflammation, and obesity are the main contributors to the initiation of T2DM. They cause chronic sterile meta-inflammation and insulin resistance, thereby making a person more susceptible to developing T2DM. Metformin, a natural cationic biguanide, is widely used as the first-line treatment of T2DM. The exact action mechanism behind the glucose-lowering effect of metformin is not clear, but, presumably, metformin utilizes a broad spectrum of molecular mechanisms to control blood glucose including decreasing intestinal glucose absorption, inhibition of the hepatic gluconeogenesis, decreasing insulin resistance, etc. Recent studies have shown that metformin exerts its effects through the inhibition of mitochondrial respiratory chain complex 1 and the AMP-activated protein kinase (AMPK) activation, but it has been identified in the other studies that AMPK is not the sole hub in metformin mode of action or there are other unknown mechanisms which are involved and yet to be explored. Therefore, here, we discuss the updated findings of the mechanism of action of metformin that contributes to the meta-inflammation and inflammaging action. It is proposed that figuring out the precise mechanism of action of metformin could improve its application in the fields of obesity, inflammation, aging, and inflammaging.

The Antidiabetic Effects and Modes of Action of the Balanites aegyptiaca Fruit and Seed Aqueous Extracts in NA/STZ-Induced Diabetic Rats.

Diabetes mellitus (DM) is a chronic metabolic disorder that threatens human health. Medicinal plants have been a source of wide varieties of pharmacologically active constituents and used extensively as crude extracts or as pure compounds for treating various disease conditions. Thus, the aim of this study is to assess the anti-hyperglycemic and anti-hyperlipidemic effects and the modes of action of the aqueous extracts of the fruits and seeds of Balanites aegyptiaca (B. aegyptiaca) in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Gas chromatography–mass spectrometry analysis indicated that 3,4,6-tri-O-methyl-d-glucose and 9,12-octadecadienoic acid (Z,Z)- were the major components of the B. aegyptiaca fruit and seed extracts, respectively. A single intraperitoneal injection of STZ (60 mg/kg body weight (b.w.)) 15 min after intraperitoneal NA injection (60 mg/kg b.w.) was administered to induce type 2 DM. After induction was established, the diabetic rats were treated with the B. aegyptiaca fruit and seed aqueous extracts (200 mg/kg b.w./day) via oral gavage for 4 weeks. As a result of the treatments with the B. aegyptiaca fruit and seed extracts, the treated diabetic-treated rats exhibited a significant improvement in the deleterious effects on oral glucose tolerance; serum insulin, and C-peptide levels; liver glycogen content; liver glucose-6-phosphatase and glycogen phosphorylase activities; serum lipid profile; serum free fatty acid level; liver lipid peroxidation; glutathione content and anti-oxidant enzyme (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) activities; and the mRNA expression of the adipose tissue expression of the insulin receptor β-subunit. Moreover, the treatment with fruit and seed extracts also produced a remarkable improvement of the pancreatic islet architecture and integrity and increased the islet size and islet cell number. In conclusion, the B. aegyptiaca fruit and seed aqueous extracts exhibit potential anti-hyperglycemic and anti-hyperlipidemic effects, which may be mediated by increasing the serum insulin levels, decreasing insulin resistance, and enhancing the anti-oxidant defense system in diabetic rats.

Glycated apolipoprotein B decreases after bariatric surgery in people with and without diabetes: A potential contribution to reduction in cardiovascular risk

Background and aimsThe causal relationship between LDL cholesterol (LDL-C) and the pathogenesis of atherosclerosis is well established. Previous studies have shown that modifications, glycation and oxidation of LDL enhance its atherogenic potential. Glycation of LDL occurs in it is main protein component, apolipoprotein B100 (ApoB). Our aim was to assess the effect of bariatric surgery on circulating glycApoB levels and understand the factors influencing changes in its circulating levels. MethodsWe measured glycApoB in 49 individuals before, 6 and 12 months after bariatric surgery. We also assessed clinical parameters, lipoproteins, markers of inflammation and glycaemia. Correlation analysis was done to understand associations between changes in variables from baseline to 12 months after surgery. ResultsReductions in glycApoB post-bariatric surgery were significant regardless of whether the patients suffered from type 2 diabetes (T2DM) or took lipid-lowering therapy. There were no significant differences in glycApoB levels at baseline and follow-up between participants with T2DM and those without. GlycApoB declined from baseline in non-diabetics at 6 months and significantly at 12 months (1.09 mg/l vs 0.63 mg/l vs 0.49 mg/l, p < 0.05), and in those with T2DM at 6 months and significantly at 12 months (1.77 mg/l vs 1.03 mg/l vs 0.68 mg/l, p < 0.05). The percentage change in glycApoB correlated (p < 0.05) with changes in glucose (ρ = 0.40), insulin (ρ = 0.41) and HOMA-IR (%) (ρ = 0.43). There were no significant associations between changes in glycApoB and changes in total serum ApoB, LDL-C, high sensitivity C-reactive protein, weight, or BMI. ConclusionsBariatric surgery reduces levels of glycApoB; this reduction is associated with decreased insulin resistance postoperatively. This potentially reflects the potent influence of obesity-related insulin resistance on lipoprotein glycation.Our observations are of potential importance in explaining the effectiveness of bariatric surgery in decreasing cardiovascular disease (CVD) risk in both T2DM and obese individuals without T2DM, as glycation of ApoB is known to be associated with increased atherogenesis.

The effects of phytochemicals and herbal bio-active compounds on tumour necrosis factor-α in overweight and obese individuals: a clinical review.

Obesity is abnormal fat accumulation in the body which acts as a risk factor for various cardiometabolic states. Adipose tissue in excess can release inflammatory factors, including TNF-α and IL-6, and suppress adiponectin production. TNF-α increases the levels of IL-6 and acute phase reactants such as C-reactive protein. Inflammation has a crucial role in developing and progressing various cardiometabolic diseases and a wide range of obesity-related complications. It has been shown that TNF-α has a significant role in the development of insulin resistance. Recently, a growing body of evidence has focused on herbal medicine, phytochemicals and natural bioactive compounds as inexpensive, relatively easy accessible agents with low adverse effects to reduce inflammatory markers such as TNF-α and simultaneously decrease insulin resistance, glucose intolerance, and dyslipidemia in obesity. The main focus of the current review is to summarize the results of the studies, which assessed the effects of phytochemicals and herbal bio-active compounds on serum TNF-α in subjects with overweight or obesity. This review suggests that herbal medicine have favorable effects on the reduction of TNF-α concentration; however, the results were not uniform for different products. Among the reviewed plants, ginger, ginseng, resveratrol, and flaxseed had more promising effects.

Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A1 Receptor Ligands.

Adenosine A1 receptor (A1R) activation, stimulating lipogenesis and decreasing insulin resistance, could be useful for metabolic syndrome management in obese subjects. Since full A1R agonists induce harmful side-effects, while partial agonists show a better pharmacological profile, we investigated the influence of two derivatives of the full A1R agonist 2-chloro-N6-cyclopentyladenosine (CCPA), C1 and C2 behaving as A1R partial agonists in animal models, on the adipogenic differentiation of stromal/stem cells (ASCs) from human subcutaneous adipose tissue, which mainly contribute to increase fat mass in obesity. The ASCs from normal-weight subjects showed increased proliferation and A1R expression but reduced adipogenic differentiation compared to obese individual-derived ASCs. Cell exposure to CCPA, C1, C2 or DPCPX, an A1R antagonist, did not affect ASC proliferation, while mainly C2 and DPCPX significantly decreased adipogenic differentiation of both ASC types, reducing the activity of glycerol-3-phosphate dehydrogenase and the expression of PPARγ and FABP-4, all adipogenic markers, and phosphorylation of Akt in the phosphatidylinositol-3-kinase pathway, which plays a key-role in adipogenesis. While requiring confirmation in in vivo models, our results suggest that A1R partial agonists or antagonists, by limiting ASC differentiation into adipocytes and, thereby, fat mass expansion, could favor development/worsening of metabolic syndrome in obese subjects without a dietary control.

GPR120 agonist ameliorated insulin resistance and improved ovarian function.

GPR120 is implicated in the regulation of glucose and lipid metabolism, and insulin resistance. In the current study, we aimed to investigate the role of GPR120 in polycystic ovary syndrome (PCOS). With the adoption of dehydroepiandrosterone, a rat model was established to simulate PCOS in vitro. mRNA and protein expression levels of GPR120 were measured using RT-qPCR and western blot, respectively. In addition, expression levels of testosterone, estradiol, luteinizing hormone and follicle-stimulating hormone, serum total cholesterol and triglyceride were assessed using the corresponding kits. Moreover, haematoxylin and eosin staining was used to detect pathological changes in ovary or liver and oil red staining was utilized to evaluate lipid accumulation. In the present study, GPR120 was downregulated in plasma, liver and ovary in the PCOS rat model. In addition, the GPR120 agonist regulated lipid metabolism in the liver and weight in the PCOS rat model. Furthermore, the GPR120 agonist decreased insulin resistance in the PCOS rat model but improved the ovarian function. It is suggested that GPR120 plays a vital role in suppressing insulin resistance, regulating ovary function and decreasing lipid accumulation in the liver, demonstrating that targeting GPR120 could be an effective method for the improvement of PCOS.

In vivo therapeutic exploring for Mori folium extract against type 2 diabetes mellitus in rats.

Background: The study was aimed to investigate the potential therapeutic effect of Mori folium aqueous extracts (MFAE) on type 2 diabetes mellitus (T2DM) in vivo.Methods and results: A rat model of T2DM was established with the combination of high sugar and high-fat diet (HSFD) and streptozotocin (STZ). The T2DM rats were administrated with low (2 g.kg−1) and high (5 g.kg−1) doses of MFAE for 60 consecutive days. The biochemical indices of glucose metabolism disorders, insulin resistance and oxidative stress were observed. The results indicated that MFAE significantly promoted the synthesis of hepatic glycogen, reduced the levels of fasting blood glucose and fasting blood insulin, and improved the insulin sensitivity index (ISI). MFAE administration also remarkably increased the levels of superoxide dismutase (SOD) and reduced the levels of malondialdehyde (MDA).Conclusion: MFAE showed a therapeutic effect on T2DM with the bioative effect of improve glucose metabolism disorders, decrease insulin resistance, and ameliorate the antioxidative ability.

ASSESSMENT OF THE EFFECT OF VITAMIN D SUPPLEMENTATION ON IMPROVING GLYCAEMIC CONTROL IN DIABETIC VITAMIN D-DEFICIENT PREGNANT WOMEN

The study is conducted to assess the effect of vitamin D supplementation in diabetic vitamin D-Deficient pregnant women on the improvement of blood sugar levels. One hundred sixty pregnant women in age ranged 18-40 years were randomized into Group I &amp; Group II. Group I am consisting of 80 patients were supplemented with 60,000 I.U of vitamin D3 and Group II were offered routine antenatal care as per institutional protocol. Mean age was 28.1 years and 28.4 years, weight was 73.5 Kgs and 74.1 kgs, height was 156.2 cms and 157.4 cms, BMI (Kg/m2) was 30.1 and 29.5, primigravida was seen in 35 and 42, multigravida in 45 and 38, overt DM in 12 and 10, H/O GDM in previous pregnancy was seen in 16 and 8 and family history of DM was seen in 36 and 24 in Group I and Group II respectively. 35 patients in Group I and 26 in Group II were on insulin which increased to 40 in Group I and 30 in Group II on post- intervention. 32 patients in Group I and 25 in Group II required metformin which increased to 36 in Group I and 28 in Group II. The difference was comparable (P&gt; 0.05) between both Groups. Vitamin D supplementation had no effect on decreasing insulin resistance or improving the blood sugar levels in diabetic pregnant women suffering from deficiency of vitamin D.

Cocoa flavonoids: a promising ingredient that potentiates vitamin d action in skeletal muscle cells

Rationale: Vitamin D (VitD) effects take place by binding to its receptor (VDR) which is a classical nuclear receptor responsible for genomic effects, but there is also a fraction of the VDR located in the muscle plasma membrane that is responsible for its non-genomic effects. In addition to the established effect of VitD in bone and mineral homeostasis, VitD insufficiency/deficiency is linked to a range of muscle disorders including frailty and muscle loss/dysfunction. Flavonoids decrease insulin resistance and have antioxidant and anti-inflammatory properties by activating Akt signaling pathways. Our study has aimed to evaluate, in VitD deficient conditions, if cocoa flavonoids (CF) are able to mediate the interacction between VitD and skeletal muscle glucose uptake by triggerring the modulation of its genomic and non-genomic signaling pathways. This could be useful in pathological deficient VitD situations, such as diabetes or sarcopenia where muscle function is compromised due to the onset of insulin resistance.

Rationale for an anti‐inflammatory insulin sensitizer in a phase 3 Alzheimer's disease trial

AbstractBackgroundNE3107 (3α‐ethynyl‐androst‐5‐ene‐3β,7β,17β‐triol), shows safety, antiinflammatory and insulin‐sensitizing activities in vitro, in animals, and humans. NE3107 binds ERK1/2 and inhibits inflammatory, but not homeostatic NFkB/ERK signaling in vitro, in animals and in humans. NE3107 is blood‐brain permeable, and does not affect neurotransmitter receptors. NE3107 inhibits TNFα‐stimulated NFκB transcription in human macrophages. It also inhibits NFκB nuclear translocation and LPS‐stimulated inflammatory signal transduction. NE3107 prevented IκBα proteolysis in murine macrophages. NE3107 decreased EAE optic nerve microglia, and increased nuclear NFκB in collicular and retinal neurons (homeostatic), but decreased optic nerve head glial nuclear NFκB (inflammatory) in a glaucoma model. NE3107 preserved dopaminergic neurons in MPTP‐treated mice and marmosets. In obese impaired glucose tolerance (IGT) humans, NE3107 decreased CRP, which is involved in AD inflammation and tissue damage, and increased antiinflammatory HDL, which decreases risk of AD pathogenesis. NE3107 increased adiponectin, which suppresses insulin resistance, inflammation, and AD pathology. In obese, inflamed IGT and type 2 diabetes (T2D) subjects, NE3107 decreased insulin resistance, which drives neurodegeneration and AD. Importantly, in obese inflamed T2D subjects, NE3107 decreased inflammation‐driven systems deregulation, known to contribute to AD progression.MethodSafety and activity data from preclinical, toxicology, human clinical trials, and a protocol synopsis for a pivotal trial in AD were submitted, and the FDA allowed NeurMedix to proceed with the NM101 trial.ResultA Phase 3, Double Blind, Randomized, Placebo Controlled, Parallel Group, Multicenter Study of NE3107 in Subjects Who Have Mild to Moderate Alzheimer's Disease (NCT04669028) will evaluate safety and efficacy of oral 20 mg BID NE3107 vs. placebo in 316 subjects with mild to moderate AD. Two coprimary outcome measures ADAS Cog12 and ADCS CGIC will be evaluated as the change from Baseline to Week 30. Secondary endpoints include measures of neuropsychological deficits, functional performance, glycemic control and resource utilization. A subset of patients may volunteer for exploratory vMRI and FDG‐PET scans at baseline and week 30.ConclusionInflammation and insulin resistance drive AD. NE3107 decreases these insults that drive systems dysregulation in AD. This trial is well‐positioned to examine the effects of NE3107 on progression of AD dementia, affecting more than 40 million people globally.