High-fructose Diet-induced Insulin Resistance Research Articles

Lactobacillus rhamnosus GG administration partially prevents diet-induced insulin resistance in rats: a comparison with its heat-inactivated parabiotic.

Insulin resistance and type 2 diabetes are obesity-related health alterations, featuring an ever-increasing prevalence. Besides inadequate feeding patterns, gut microbiota alterations stand out as potential contributors to these metabolic disturbances. The aim of this study was to investigate whether the administration of a probiotic (Lactobacillus rhamnosus GG) effectively prevents diet-induced insulin resistance in rats and to compare these potential effects with those exerted by its heat-inactivated parabiotic. For this purpose, 34 male Wistar rats were fed a standard or a high-fat high-fructose diet, alone or supplemented with viable or heat-inactivated Lactobacillus rhamnosus GG. The body and white adipose tissue weight increases, induced by the obesogenic diet, were prevented by probiotic and parabiotic administration. The trend towards higher basal glucose levels and significantly higher serum insulin concentration observed in the non-treated animals fed with the obesogenic diet were effectively reverted by both treatments. Similar results were also found for serum adiponectin and leptin, whose levels were brought back by the probiotic and parabiotic administration to values similar to those of the control animals. Noteworthily, parabiotic administration significantly reduced skeletal muscle triglyceride content and activated CPT-1b compared to the non-treated animals. Finally, both treatments enhanced Akt and AS160 phosphorylation in the skeletal muscle compared to the non-treated animals; however, only parabiotic administration increased GLUT-4 protein expression in this tissue. These results suggest that heat-inactivated Lactobacillus rhamnosus GG seem to be more effective than its probiotic of origin in preventing high-fat high-fructose diet-induced insulin resistance in rats.

Metformin alleviates long-term high-fructose diet-induced skeletal muscle insulin resistance in rats by regulating purine nucleotide cycle

Nutrient excess caused by excessive fructose intake can lead to insulin resistance and dyslipidemia, which further causes the development of metabolic syndrome. Metformin is a well-known AMPK activator widely used for the treatment of metabolic syndrome, while the mechanism of AMPK activation remains unclear. The present study aimed to investigate the pharmacological effects of metformin on fructose-induced insulin resistance rat, and the potential mechanism underlying AMPK activation in skeletal muscle tissue. Results indicated that metformin significantly ameliorated features of insulin resistance, including body weight, Lee's index, hyperinsulinemia, dyslipidemia, insulin intolerance and pancreatic damage. Moreover, treatment with metformin attenuated the inflammatory response in serum and enhanced the antioxidant capacity in skeletal muscle tissue. The therapeutic effects of metformin on fructose-induced insulin resistance may be related to the activation of AMPK to regulate Nrf2 pathway and mitochondrial abnormality. Additionally, metformin suppressed the expression of adenosine monophosphate deaminase 1 (AMPD1) and up-regulated the expression of adenylosuccinate synthetase (ADSS) in the purine nucleotide cycle (PNC), which facilitated the increase of AMP level and the ratio of AMP/ATP. Therefore, we proposed a novel mechanism that metformin activated AMPK via increasing AMP by regulating the expression of AMPD1 and ADSS in PNC pathway.

Clerodendrum trichotomum extract improves metabolic derangements in high fructose diet-fed rats

ABSTRACT Clerodendrum trichotomum has been reported to possess beneficial properties for human health, but its effects on metabolic syndrome have not been reported. In this study, we investigated the effect of C. trichotomum leaf extract (CT) on the metabolic derangements induced by a high-fructose (HF) diet. Sprague–Dawley rats were fed with a 46% carbohydrate diet (HC group), 60% high-fructose diet (HF group), or HF diet supplemented with CT (500 mg/kg of body weight/day, CT group) via drinking water for 16 weeks. Results showed that CT alleviated HF diet-induced insulin resistance, dyslipidemia, and hepatic steatosis In liver tissues, CT affected the signaling pathways of AMP-activated protein kinase, peroxisome proliferator-activated receptor α (PPARα), and sterol regulatory element binding protein 1. CT enriched the genes that were mainly involved in cytokine-cytokine receptor interaction, PPAR, PI3K-Akt signaling pathways, and fatty acid metabolism pathway. These results suggest that CT is a promising therapeutic against metabolic disorders.

Sirt1 and Sirt3 Activation Improved Cardiac Function of Diabetic Rats via Modulation of Mitochondrial Function.

In the present study, we aimed to evaluate the effect of Sirt1, Sirt3 and combined activation in high fructose diet-induced insulin resistance rat heart and assessed the cardiac function focusing on mitochondrial health and function. We administered the Sirt1 activator; SRT1720 (5 mg/kg, i.p.), Sirt3 activator; Oroxylin-A (10 mg/kg i.p.) and the combination; SRT1720 + Oroxylin-A (5 mg/kg and 10 mg/kg i.p.) daily from 12th week to 20th weeks of study. We observed significant perturbations of most of the cardiac structural and functional parameters in high fructose diet-fed animals. Administration of SRT1720 and Oroxylin-A improved perturbed cardiac structural and functional parameters by decreasing insulin resistance, oxidative stress, and improving mitochondrial function by enhancing mitochondrial biogenesis, OXPHOS expression and activity in high fructose diet-induced insulin-resistant rats. However, we could not observe the synergistic effect of SRT1720 and Oroxylin-A combination. Similar to in-vivo study, perturbed mitochondrial function and oxidative stress observed in insulin-resistant H9c2 cells were improved after activation of Sirt1 and Sirt3. We observed that Sirt1 activation enhances Sirt3 expression and mitochondrial biogenesis, and the opposite effects were observed after Sirt1 inhibition in cardiomyoblast cells. Taken together our results conclude that activation of Sirt1 alone could be a potential therapeutic target for diabetes-associated cardiovascular complications.

Potentiation of incretin hormones and modulation of metabolic enzymes as possible mechanisms behind the insulin sensitizing effects of cabbage-metformin treatment

In our study, we treated high fructose diet-induced insulin resistance in rats with any of metformin, cabbage (80%w/w) or combined metformin and cabbage (MetCabb), and observed the activities of glycolysis and gluconeogenesis regulatory enzymes, incretin hormones and other hormones affecting glucose homeostasis. Comparisons were made with normoglycemic noninsulin resistance rats (control) and insulin-resistant untreated rats (INres). Baseline analysis showing elevated fasting blood sugar (>250 mg/dl), insulin (>25 µIU/ml) and HOMA-IR (>10) satisfied the criteria for recruitment into the insulin-resistant groups. Treatment lasted for 12 weeks. HOMA-IR values significantly (P < 0.05) decreased from 24.7 to 5.5 and 10.6 respectively with MetCabb treatment. MetCabb normalized HOMA-IR values and mean β-cell responsiveness of the INres. Cabbage and metCabb normalized the leptin levels relative to control. The mean fasting blood sugar, insulin, and c-peptide levels with MetCabb treatment reverted to control levels. We found a strong positive linear correlation between the glucagon levels (r = 0.9145) and increasing HOMA-IR values while both incretin hormones; GLP-1 and GIP negatively regressed (r = -0.8084 and -0.8488). MetCab treatment produced comparable values of GLP-1 and GIP to the control. A strong positive correlation was found between the HOMA-IR values and the PEPCK (r = 0.9065), F-1,6-BPase (r = 0.7951), and G-6-Pase (r = 0.7893). The hexokinase (r = -0.807), PFK (r = -0.9151), and PK (r = -0.7448) levels regressed as HOMA-IR values increased. The glycolytic and gluconeogenic enzymes except PEPCK reverted to control levels with MetCabb treatment. Combination of metformin and cabbage was more effective than individual treatments.

Anti-diabetic effects of pomegranate extracts in long-term high fructose-fat fed rats

BackgroundA high-sugar or/and high-fat diets is a major risk factors for obesity. However, increased fruit and vegetable intake has been recently linked to obesity prevention. The aim of the present study was to investigate the preventive effects of pomegranate leaves (PL), juice (PJ) and peel (PP) extracts, on insulin resistance and oxidative stress in high fat and high fructose diet-induced obese rats.MethodsObesity in rats was induced by consumption of diet high in saturated fat and fructose (HFD) for a long period (12 weeks).ResultsCompared to the control group (CG) fed chow died, the high fat and high fructose diet (HFD) group showed a significant increase in the fasted plasma levels of glucose (29.8%), insulin (45%), amylase (70%) and lipase (54%). Moreover, HFD feeding has increased lipid peroxidation and protein carbonylation and decreased antioxidant enzymes levels. However, PL, PJ and PP treatment markedly prevents glucose intolerance, insulin resistance and oxidative stress and decrease amylase and lipase levels.ConclusionThese findings highlight that a long-term intake of pomegranate extracts might be a potential alternative strategy for the prevention of a HFD induced insulin resistance and oxidative stress.

Mitigation of renal inflammation and endoplasmic reticulum stress by vildagliptin and statins in high-fat high-fructose diet-induced insulin resistance and renal injury in rats

Dyslipidemia and insulin resistance in obesity can lead to lipotoxicity and cellular damage. Renal lipotoxicity in association with an impairment of lipid metabolism induces renal damage through the activation of inflammation, ER stress, fibrosis and apoptosis. We investigated the effects of a combination treatment of the DPP-4 inhibitor vildagliptin and atorvastatin on renal lipotoxicity related to renal dysfunction and injury in a high-fat high-fructose diet (HFF)-induced insulin resistant condition. Male Wistar rats were fed on a high-fat diet and were given drinking water with 10% fructose for 16 weeks. After that, rats were divided into: no treatment (HFF), treatment with vildagliptin, atorvastatin and vildagliptin plus atorvastatin for 4 weeks. The results demonstrated that the combination treatment prominently improved insulin resistance, dyslipidemia and kidney morphological changes induced by HFF. These changes correlated well with the increased expression of nephrin and podocin and decreased urine protein. Notably, the combined treatment produced greater improvement in renal lipid metabolism through increasing fatty acid oxidation with the decreases in fatty acid transporters and fatty acid synthesis, thereby reducing renal lipid accumulation in HFF rats. The reduction in renal lipotoxicity via diminishing renal inflammation, ER stress, fibrosis and apoptosis was also more significant in the combined treatment group than in the other groups in which the drug was used as a monotherapy. In conclusion, the combination therapy produced synergistic beneficial effects on metabolic parameters, lipid metabolism and accumulation related to renal lipid accumulation-induced lipotoxicity and kidney injury in the HFF-induced insulin resistant model with improved outcomes.

Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats

Background: The use of high-fructose (Fr) corn sweeteners and sucrose in manufactured food has markedly increased recently. This excessive Fr intake has been proposed in the etiology of the metabolic syndrome, which shows an increasing prevalence throughout the world. Objective: In this study, we questioned whether fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR)-α agonist, and pioglitazone (PG), a PPAR-γ agonist, might be effective in ameliorating the metabolic syndrome in a rat model. Materials and Methods: The metabolic syndrome was induced by feeding rats a high-Fr (60%) diet for 10 weeks. The rats were divided into 5 groups: control group, fed a normal rat chow; Fr + vehicle group; Fr + FF group; Fr + PG group; and Fr + (FF + PG) group (treated with both drugs). Drug or vehicle treatment was given daily for 6 weeks (from weeks 5 to 10). Thereafter, blood and liver samples were obtained for biochemical studies. Results: Rats fed a high-Fr diet developed hyperglycemia, hyperinsulinemia, hyperuricemia, hypertriglyceri­demia, and hypercholesterolemia, and had increased serum alanine aminotransferase, hepatic tumor necrosis factor-α, and malondialdehyde levels but decreases in both glutathione content and superoxide dismutase activity. Rat treatment with FF and/or PG attenuated these alterations. The improvement was greater with the combined treatment than with either drug alone, and normalization of insulin sensitivity was observed only in rats treated with the combination therapy. Conclusion: Acting on the 2 main PPAR subfamilies, the combination of FF and PG provides a more efficacious therapy for modulating the changes in serum insulin, uric acid, and lipids, as well as the accompanying hepatic inflammation and oxidative stress that characterize the Fr-induced metabolic syndrome.

Dietary chokeberry and dried jujube fruit attenuates high-fat and high-fructose diet-induced dyslipidemia and insulin resistance via activation of the IRS-1/PI3K/Akt pathway in C57BL/6\u2009J mice

BackgroundThe incidence of metabolic syndrome linked to dyslipidemia and insulin resistance has increased; thus, studies must be conducted to elucidate this phenomenon. The present study aimed to investigate the protective effects of chokeberry and dried jujube diet on high-fat and high-fructose diet-induced dyslipidemia in mice.MethodsMale C57BL/6 J mice were divided into five groups: ND, mice fed normal diet and tap water; HFFD, mice fed 60% high-fat and 10% fructose diet (HFFD) in tap water; HFFD+C, mice fed HFFD with 1% chokeberry powder; HFFD+J, mice fed HFFD with 1% jujube fruit powder; and HFFD+M, mice fed HFFD with 0.5% chokeberry + 0.5% jujube fruit powder mixture.ResultsAfter 10 weeks of dietary treatment, chokeberry and dried jujube fruits reduced HFFD-induced weight gain and central obesity and decreased liver weight and abdominal and epididymal fat mass. Furthermore, such fruits attenuated HFFD-induced dyslipidemia; decreased triglyceride, total cholesterol, non-high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and very-low-density lipoprotein-cholesterol levels. Insulin resistance was improved via the consumption of dietary chokeberry and dried jujube fruits according to various indicators (serum insulin level, fasting blood glucose level, homeostatic model assessment-insulin resistance score, and oral glucose tolerance test value). These treatments were found to lower serum triglyceride levels. Moreover, the consumption of chokeberry and dried jujube changed the hepatic protein expression of insulin receptor, insulin receptor substrate 1, phosphoinositide 3-kinase, Akt, and catalase, which are associated with insulin resistance.ConclusionsChokeberry and dried jujube could be used in the management of dyslipidemia and insulin resistance associated with metabolic syndrome by reducing risk parameters in mice with HFFD.

Rice bran oil ameliorates hepatic insulin resistance by improving insulin signaling in fructose fed-rats.

Insulin resistance is an inadequate metabolic response of the peripheral tissue to circulating insulin. It plays an important pathophysiological role in type 2 diabetes mellitus. The purpose of the study was to investigate the molecular effects of rice bran oil (RBO) on the gene expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), glucose transporters-4 and 5 (GLUT-4 and 5) in insulin-resistant rats induced by high fructose diet (HFD). Rats were divided into six groups (10 rats each) as follows: Groups 1 and 2: rats received a standard diet with corn oil or RBO (as the sole source of fat), respectively. Group 3: animals fed on HFD, which was furtherly divided into 2 sub-groups: rats fed HFD either for one (HFD1) or for 2months (HFD2). Group 4, rats fed HFD containing RBO for 1 month (HFD1 + RBO), while rats in group 5 fed HFD for 30days then RBO was added to the diet for another 30days (HFD2 + RBO). Serum levels of glucose and insulin, as well as hepatic gene expression of insulin receptors and glucose transporters were determined. Livers were isolated for histopathological study. HFD induced insulin resistance with a reduction in the hepatic level of insulin receptor and glucose transporters at both protein and molecular levels. Addition of RBO improved the insulin sensitivity and up-regulated the expression of the tested genes. HFD impaired the insulin sensitivity of the hepatocytes by down-regulating the insulin receptor genes. Addition of RBO alleviated all the hazardous effects.

EVALUATION OF REVERSAL EFFECTS OF EUGENIA JAMBOLANA SEED EXTRACTS AGAINST HIGH-FRUCTOSE DIET-INDUCED INSULIN RESISTANCE IN ALBINO RATS

Objective: The objective of this study is to evaluate the reversal effects of aqueous and ethanolic extracts of jamun seeds against high-fructose (HFr) diet-induced insulin resistance (IR) in albino rats.Methods: Thirty male albino rats were divided into five groups (n=6), and all the group rats except normal control were provided with HFr (60% w/v) to their drinking water daily for 42 days. Group 1 and 2 served as a normal and fructose control. Groups 3, 4, and 5 were supplemented with metformin (MET 500mg/kg p.o) and aqueous and ethanolic extracts of jamun seeds (Jamun seed aqueous extract [JSAE] and Jamun seed ethanolic extract [JSEE] 1000 mg/kg of each p.o), from day 28 to day 42, respectively. Physical (body weights, food, and water intake) and biochemical (glucose, insulin, and lipid) parameters were estimated, and Homeostasis model assessment (HOMA)-IR values were calculated.Results: HFr diet significantly (p&lt;0.05) increased weight gain and water intake with decreased food intake in rats. HFr-fed rats exhibited a significant (p&lt;0.05) increase in fasting glucose, insulin, and lipid levels along with increased HOMA-IR values and confirms the development of IR. Supplementation with MET, JSAE, and JSEE significantly (p&lt;0.05) restored the physical parameters and reversed fasting glucose and lipid levels in comparison with HFr control. Whereas, only JSAE had significantly reversed the fasting insulin levels in comparison with HFr control. HOMA-IR values were significantly (p&lt;0.05) decreased in both the extract groups of HFr-fed rats, and the results were comparable to MET.Conclusion: Our study concludes that both aqueous and ethanolic extracts of jamun exhibit a significant reversal effect against HFr diet-induced IR, due to insulin-sensitizing actions at the target tissues.

P9 - Plant Bioactives and the Intestinal Barrier: Redox Signaling and Implications for Insulin Resistance

Dietary plant bioactives, and in particular flavonoids, can exert actions at the gastrointestinal (GI) tract that can have an impact systemically, e.g. on glucose homeostasis, lipid and energy metabolism. GI barrier permeabilization and the associated increased passage to the circulation of luminal endotoxins underlie in part the pathophysiology of obesity-associated pathologies, including insulin resistance and type 2 diabetes. Endotoxins trigger systemic pro-inflammatory responses that contribute to tissue insulin resistance involving the activation of redox-regulated signals. Among flavonoids, we found that the flavan-3-ol (-)-epicatechin (EC) inhibits high fat (HFD)- and/or high fructose (HFr) diet-induced insulin resistance and steatosis in rodents. These beneficial effects are associated with EC capacity to inhibit HFD-mediated intestinal barrier permeabilization and endotoxemia. In vivo and in vitro studies support intestinal cell NADPH oxidase as a major target involved in EC effects. NADPH oxidase triggers a downstream series of events that cause tight junction disruption: NF-kB and ERK1/2 activation, upregulation of myosin light chain (MLC) kinase, leading to MLC phosphorylation and consequent monolayer permeabilization. Modulation of NADPH oxidase is also involved in the capacity of EC to restore insulin sensitivity in liver and adipose tissues, given that the redox-regulated activation of IKK/NF-kB, JNK1/2 and PKC causes inhibitory serine phosphorylation of the insulin receptor (IR) substrate 1 (IRS1), and upregulation of the IR and IRS1 inhibitory tyrosine phosphatase PTP1B. EC and other structurally related flavonoids (i.e. anthocyanidins (AC)) that directly inhibit NADPH oxidase, share similar chemical structures and capacity to improve insulin sensitivity. Furthermore, inhibition of NF-kB can explain EC-mediated decreased expression of select NADPH isoforms. In summary, the capacity of select bioactives (EC, AC) to improve HFD/HFR-associated insulin resistance is in part mediated through their capacity to modulate NADPH oxidase and redox-regulated pathways, leading to loss of GI tract barrier integrity and downregulation of the insulin pathway.

Polysaccharides extracted from Phellinus linteus ameliorate high-fat high-fructose diet induced insulin resistance in mice

Phellinus linteus polysaccharide (PLP) has hypoglycemic effects, but mechanisms remain unclear. Male C57BL/6 J mice were either fed a normal diet (CON) or a high-fat high-fructose diet (HFD) for 16 weeks, and starting from week 12, HFD-fed animals in PLP group were orally given PLP. PLP administration significantly reduced fasting blood glucose level and ameliorated glucose intolerance. Differentially expressed genes involved in FOXO signaling pathway and in vitamin B12 (VB12) transport were identified between HFD and PLP group. HFD decreased the phosphatidylcholine (PC) to phosphatidylethanolamine (PE) ratio and S-adenosyl methionine to S-adenosyl homocysteine ratio, which were recovered by PLP treatment. Plasma VB12 levels in HFD group was lower than CON or PLP group, and PLP stimulated the proliferation of gut bacteria in genus Porphyromonas with capability of VB12 synthesis. In conclusion, PLP administration improved insulin resistance via modifying hepatic phospholipids metabolism and rescuing insulin signaling transduction.

Trigonelline attenuates hepatic complications and molecular alterations in high-fat high-fructose diet-induced insulin resistance in rats.

The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines. Histopathological and DNA cytometry examinations were carried out for hepatic and pancreatic tissues. Hepatic tissues were examined using Fourier-transform infrared spectroscopy for assessment of any molecular changes. Results of the present study revealed that oral treatment of insulin-resistant rats with TRG or TRG in combination with SIT significantly decreased homeostatic model assessment of IR, hepatic lipids, oxidative stress biomarkers, and the inflammatory cytokines. TRG or TRG in combination with SIT ameliorated the histopathological, DNA cytometry, and molecular alterations induced by a HFHF diet. Finally, it can be concluded that TRG has beneficial effects on the hepatic complications associated with IR due to its hypoglycemic effect and antioxidant potential.

Selenium-containing polysaccharides from Ziyang green tea ameliorate high-fructose diet induced insulin resistance and hepatic oxidative stress in mice.

The present study was designed to evaluate the effects of selenium-containing tea polysaccharides (Se-GTP) from a new variety of selenium-enriched Ziyang green tea against high fructose (HF)-induced insulin resistance and hepatic oxidative stress in mice. Healthy male Kunming mice were fed 20% high fructose water and administered 200, 400 and 800 mg per kg bw Se-GTP for 8 weeks. Mice fed HF in drinking water displayed significant insulin resistance, hepatic steatosis and oxidative stress observed by hyperglycemia and hyperinsulinemia, as well as increases in hepatic non-esterified fatty acid (NEFA) and malonaldehyde (MDA). The administration of Se-GTP at 400 and 800 mg per kg bw significantly improved insulin sensitivity, and reduced liver steatosis and oxidative stress damage, and brought back the antioxidants and hepatic lipids towards near-normal values. In the oral glucose tolerance test, the administration of Se-GTP at 400 and 800 mg per kg bw had reduced plasma glucose concentrations after 30 min of glucose loading in HF-fed mice, suggesting that Se-GTP improved glucose intolerance. Histopathological examination indicated that the impaired pancreatic/hepatic tissues were effectively restored in HF-fed mice following the Se-GTP treatment. This is the first report showing that Se-GTP can ameliorate the high fructose-induced insulin resistance and hepatic oxidative injury.

Restoration of autophagy alleviates hepatic ER stress and impaired insulin signalling transduction in high fructose-fed male mice.

High-carbohydrate (mainly fructose) consumption is a major dietary factor for hepatic insulin resistance, involving endoplasmic reticulum (ER) stress and lipid accumulation. Because autophagy has been implicated in ER stress, the present study investigated the role of autophagy in high-fructose (HFru) diet-induced hepatic ER stress and insulin resistance in male C57BL/6J mice. The results show that chronic HFru feeding induced glucose intolerance and impaired insulin signaling transduction in the liver, associated with ER stress and the accumulation of lipids. Intriguingly, hepatic autophagy was suppressed as a result of activation of mammalian target of rapamycin. The suppressed autophagy was detected within 6 hours after HFru feeding along with activation of both inositol-requiring enzyme 1 and protein kinase RNA-like endoplasmic reticulum kinase pathways. These events occurred prior to lipid accumulation or lipogenesis and were sufficient to blunt insulin signaling transduction with activation of c-Jun N-terminal kinase/inhibitory-κB kinase and serine phosphorylation of insulin receptor substrate 1. The stimulation of autophagy attenuated ER stress- and c-Jun N-terminal kinase/inhibitory-κB kinase-associated impairment in insulin signaling transduction in a mammalian target of rapamycin -independent manner. Taken together, our data suggest that restoration of autophagy functions disrupted by fructose is able to alleviate ER stress and improve insulin signaling transduction.

Chemical composition of Pleurotus eryngii polysaccharides and their inhibitory effects on high-fructose diet-induced insulin resistance and oxidative stress in mice.

High intake of dietary fructose exerts a number of adverse metabolic effects. The present study investigates the preventive effects of Pleurotus eryngii polysaccharides (PEP), which showed powerful antioxidant activity in vitro, on insulin resistance and oxidative stress in mice fed a high-fructose diet. PEP was identified by HPLC as the heteropolysaccharides with d-glucose (62.8%, mol%), d-galactose (24.4%) and d-mannose (9.8%) being the main component monosaccharides. Mice fed 20% fructose in drinking water for 6 weeks significantly displayed hyperglycemia, hyperinsulinemia, dyslipidemia and liver oxidative stress with impaired insulin sensitivity (p < 0.05). The administration of PEP at 400 and 800 mg kg(-1) bw significantly reduced the fasting serum glucose and insulin concentrations and lipid deposition in HF-fed mice, and caused the reduction of liver lipid peroxidation and the elevation of the hepatic antioxidant system. The histopathology of the liver by conventional H&E and oil red O staining confirmed the liver steatosis induced by a HF diet and the hepatoprotective effect of PEP. These results suggest that Pleurotus eryngii is a potential source of polysaccharides, and might be regarded as a novel preventive and therapeutic product for the mitigation of insulin resistance, oxidative stress and liver dysfunction.

Levocetirizine ameliorates high fructose diet-induced insulin resistance, vascular dysfunction and hepatic steatosis in rats

This study investigates the possible protective effects of levocetirizine against fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction, in comparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley rats (150–200g) were divided into 4 groups. Three groups were fed on high fructose diets (HFD) containing 60% w/w fructose, while the fourth control group was fed on standard laboratory food for 8 weeks. AUCOGTT, AUCITT, fasting glucose, HOMA-IR, hepatic glutathione (GSH) and malondialdehyde (MDA) levels, serum total cholesterol, LDL-C, C-reactive protein (CRP) level and lactate dehydrogenase (LDH) activity and liver steatosis scores were significantly higher in HFD group compared to control group. Moreover, body weight gain, food intake, feeding efficiency, HOMA-β, Emax and pEC50 of acetylcholine-induced relaxations of aortic rings and hepatic superoxide dismutase (SOD) activity were significantly lower in HFD group than in control group. Treatment with levocetirizine caused significant decreases in AUCOGTT, AUCITT, HOMA-IR, hepatic GSH and MDA levels and serum CRP level and LDH activity and significant increases in hepatic SOD activity and HOMA-β when compared with the HFD group. Although levocetirizine failed to alter TC and LDL-C levels, it produced a significant increase in HDL-C level relative to control group. Levocetirizine was also able to improve acetylcholine-induced relaxations of aortic rings, indicating a protective effect against insulin resistance-induced endothelial damage comparable to that offered by pioglitazone. Moreover, levocetirizine substantially attenuated insulin resistance-associated liver macrovesicular steatosis. These findings demonstrate that levocetirizine ameliorates insulin resistance, improves glucose tolerance and attenuates insulin resistance-linked hepatic steatosis and vascular damage.

Protective effect of umbelliferone on high-fructose diet-induced insulin resistance and oxidative stress in rats

The present study was designed to investigate the effect of umbelliferone (UMB) on insulin resistance (IR) and oxidative stress in rats fed a high fructose diet (HFD). Male Wistar rats received a daily diet containing either 60% fructose or 60% starch. They were administered with the UMB at three different doses (10, 20 and 40mg/kg, p.o) from the 16th day. At the end of 60 days, HFD rats exhibited significant increases in plasma glucose and insulin levels. The activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and the levels of non-enzymic antioxidants such as vitamin C, vitamin E and reduced glutathione were decreased while increases in the levels of lipid peroxidative markers were observed in liver tissues of HFD rats as compared to control rats. In addition, rats fed a HFD with UMB reversed all the above changes to near normal in a dose dependent manner. The effect at a dose of 40mg/kg b.w/day was more pronounced than the other two doses (10 and 20mg/kg b.w/day). Biochemical findings were supported by histological studies. These results indicated that administration of UMB may be a feasible therapeutic strategy for prevention of a high-fructose diet-induced insulin resistance and oxidative stress.

Amla (Emblica officinalis) extract is effective in preventing high fructose diet–induced insulin resistance and atherogenic dyslipidemic profile in ovariectomized female albino rats

The aim of this study was to evaluate the effect of ovarian hormone withdrawal and a high fructose diet on the development of atherogenic dyslipidemia in rats. Because amla (Indian gooseberry) is known to possess hypolipidemic properties, its preventive effect on the above was also studied. Three-month-old female albino rats were either ovariectomized (n = 48) or sham-operated (n = 12). The study was performed in two phases: phase 1 (first 12 wk) and phase 2 (next 6 wk). The sham-operated rats were fed rodent chow in both phases (control). The ovariectomized rats were assigned to four groups: rats fed chow in both phases (O), rats fed a 60% fructose-rich diet in phase 2 alone (O + F), rats administered chow and amla extract in both phases (O + A), and rats administered chow + amla extract in phase 1 and then fed a 60% fructose-rich diet + amla extract in phase 2 (O + F + A). O + F rats developed insulin resistance and had increased triglycerides (TGs) and total cholesterol. O + A and O + F + A groups had significantly lower low-density lipoprotein cholesterol and higher high-density lipoprotein (HDL) cholesterol compared with controls. O + F + A did not develop insulin resistance and had reduced TGs compared with O + F rats. O + A and O + F + A rats showed a tremendous decrease in non-HDL cholesterol and non-HDL cholesterol/HDL cholesterol, TG/HDL cholesterol, and total cholesterol/HDL cholesterol ratios. Amla decreased low-density lipoprotein cholesterol and increased HDL cholesterol in ovariectomized rats fed chow or fructose. In ovariectomized and fructose-fed rats, it prevented insulin resistance aside from subduing the rise in TG. Amla may be explored for its use in preventing dyslipidemia in postmenopausal women.