High Fructose-induced Insulin Resistance Research Articles

Lycium barbarum leaf flavonoids ameliorate high fructose induced insulin resistance in mice by regulating blood glucose and gut microbiota composition

Insulin resistance is an increasingly severe public health issue worldwide, affecting millions and significantly raising the risk of diabetes and cardiovascular diseases. Despite this, current treatment options remain limited, which has heightened interest in exploring interventions based on natural compounds. This study investigates the potential of Lycium barbarum leaf flavonoids (LBLF) to improve insulin resistance induced by high fructose in mice, with a focus on the mechanisms related to blood glucose regulation and gut microbiota composition. Research results show that, compared to the high fructose model group, treatment with metformin hydrochloride and rutin reduced fasting blood glucose levels by 32.06% and 18.94%, respectively. LBLF treatment at various doses decreased fasting blood glucose levels by 12.29%, 19.02%, and 32.98%, and insulin levels by 26.50%, 11.04%, and 28.23%, respectively, demonstrating its effective ability to regulate blood glucose levels. It was also found that LBLF effectively regulated lipid disorders, significantly reduced oxidative stress in the liver, and protected liver function. Liver transcriptomic analysis suggests that LBLF may improve insulin resistance by regulating gene expression in the MAPK and retinol metabolism signaling pathways. Additionally, gut microbiota diversity analysis revealed that LBLF treatment reduced the Firmicutes/Bacteroidetes (F/B) ratio, which is associated with obesity and metabolic disorders, thereby optimizing the gut microbiota structure disrupted by high fructose intake. These results highlight the therapeutic potential of LBLF in managing insulin resistance and associated metabolic disorders, providing a theoretical basis for further research into its broader applications.

Protective Effect of Hydroalcoholic Extract of Punica granatum Leaves on High Fructose Induced Insulin Resistance in Experimental Animals.

Insulin resistance (IR) is a condition characterized by reduced sensitivity of body tissues to insulin, leading to impaired regulation of downstream metabolic pathways and elevated blood glucose levels. Diets rich in fructose have been proven to cause insulin resistance in test rats, resulting in decreased insulin sensitivity, particularly in the liver, and compromised disposal of glucose from the body. In the search for effective treatments, Plant-derived formulations have gained popularity because to their ability for treating a variety of ailments. One such plant is Punica granatum Linn. from the Punicaceae family, which has long been used in the treatment of diabetes and its consequences. This study investigates the insulin-resistant activity of an extract from Punica granatum leaves. The study goal is to assess the possible protective role of Punica granatum against insulin resistance through various analyses, including serum glucose and insulin levels, lipid profile assessment, measurement of liver enzymes (ALP, SGOT, SGPT), and histopathological examination of liver sections. The study involves several key methods to evaluate the insulin-resistant activity of Punica granatum extract in high fructose diet induced insulin resistance animal model. The extract was administered orally to the experimental animals. These methods include the measurement of serum glucose and serum insulin levels, analysis of the lipid profile, quantification of liver enzymes such as ALP, SGOT, and SGPT, and a detailed histopathological examination of liver tissue sections. These analyses collectively provide insights into the impact of Punica granatum extract on insulin resistance and related metabolic parameters. Findings of this study provide insight on the possible benefits of Punica granatum extract on insulin resistance. Through the assessment of serum glucose and insulin levels, lipid profile analysis, and measurement of liver enzymes, the study elucidates the impact of the extract on key metabolic indicators. Additionally, the histopathological examination of liver sections provides visual insights into the structural changes that may occur as a result of the treatment. In conclusion, this study highlights the ability of Punica granatum extract as a candidate for addressing insulin resistance. The findings suggest that the extract may have a protective role against insulin resistance, as evidenced by improvements in serum glucose and insulin levels, lipid profile, liver enzyme levels, and histopathological characteristics. Further research and investigations are warranted to fully understand the mechanisms underlying these observed effects and to validate the potential of Punica granatum extract as a therapeutic option for managing insulin resistance and its associated complications.

Correlation between brain neurotransmitters and insulin sensitivity: Neuro-preservative role of resveratrol against high fat, high fructose-induced insulin resistance

The development of obesity and prediabetes under conditions of long-term consumption of fructose solution in ratsVictoria Konopelnyuk, Alona Yurchenko, Taras Karpovets, Ludmila Ostapchenko

Tartary buckwheat flavonoids ameliorate high fructose-induced insulin resistance and oxidative stress associated with the insulin signaling and Nrf2/HO-1 pathways in mice.

The present study was conducted to explore the effects of a purified tartary buckwheat flavonoid fraction (TBF) on insulin resistance and hepatic oxidative stress in mice fed high fructose in drinking water (20%) for 8 weeks. The results indicated that continuous administration of TBF dose-dependently improved the insulin sensitivity and glucose intolerance in high fructose-fed mice. TBF treatment also reversed the reduced level of insulin action on the phosphorylation of insulin receptor substrate-1 (IRS-1), protein kinase B (Akt) and phosphatidylinositol 3-kinase (PI3K), as well as the translocation of glucose transporter type 4 (GLUT4) in the insulin-resistant liver. Furthermore, TBF was found to exert high antioxidant capacity as it acts as a shield against oxidative stress induced by high fructose by restoring the antioxidant status, and modulating nuclear factor E2 related factor 2 (Nrf2) translocation to the nucleus with subsequently up-regulated antioxidative enzyme protein expression. Histopathological examinations revealed that impaired pancreatic/hepatic tissues were effectively restored in high fructose-fed mice following TBF treatment. Our results show that TBF intake is effective in preventing the conversion of high fructose-induced insulin resistance and hepatic oxidative stress in mice by improving the insulin signaling molecules and the Nrf2 signal pathway in the liver.

NFAT inhibitor tributylhexadecylphosphoniumbromide, ameliorates high fructose induced insulin resistance and nephropathy

High fructose diet (HFrD)-induced insulin resistance (IR) has been reported to be associated with an increase in albuminuria, glomerular hypertrophy and inflammation in kidney. However, the molecular mechanisms associated with high fructose-induced IR and renal dysfunction are still unclear. In the present study, we have investigated the role of nuclear factor of activated T-cell (NFAT) and its inhibitor, Tributylhexadecylphosphoniumbromide (THPB) in high fructose-induced IR and renal injury. NFAT inhibition by THPB treatment significantly improved HFrD-induced insulin resistance. Treatment with THPB markedly reduced high fructose diet-induced protein expression of NFATc4, PTEN and also alleviated expression of inflammatory markers in kidneys of HFrD rats. Further, THPB treatment not only improved acute ANG II responses but also repressed the processes of renal fibrosis, ECM accumulation, foot process effacement and renal apoptosis in HFrD rats. Taken together, we for the first time provide evidence that HFrD -induced insulin resistance and renal injury is associated with dysregulated NFATc4/PTEN signalling and THPB prevents this dysregulation through inhibition of NFATc4. Thus, targeting NFATc4 can be a novel therapeutic approach for preventing HFrD induced- IR and renal injury.

Preventive effects of jujube polysaccharides on fructose-induced insulin resistance and dyslipidemia in mice.

High fructose intake is associated with adverse metabolic syndromes. This study was designed to investigate whether the polysaccharides derived from Zizyphus jujube cv. Shaanbeitanzao (ZSP) could alleviate high fructose-induced insulin resistance and dyslipidemia in mice. ZSP was identified by capillary zone electrophoresis as an acidic heteropolysaccharide with l-arabinose, d-galactose and d-galacturonic acid being the main component monosaccharides. Mice were provided with 20% high-fructose water and ZSP was administered intragastrically at doses of 0, 200 or 400 mg kg(-1) BW for 4 weeks. Fructose-treated mice showed hyperglycemia, hyperinsulinemia and dyslipidemia with impaired insulin sensitivity (p < 0.05). Administration of ZSP at a dose of 400 mg kg(-1) BW significantly reduced the serum levels of glucose, insulin, TC, TG, LDL-C, and VLDL-C (p < 0.01). ZSP also markedly improved the HDL-C level, homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), and decreased the atherogenic index (AI) of the mice exposed to high-fructose water. Histopathological test with H&E and oil red O staining confirmed liver steatosis induced by a high-fructose diet and the hepatoprotective effect of ZSP. These findings indicate that the jujube polysaccharides may ameliorate insulin resistance and dyslipidemia in fructose-treated mice.

An integrated metabonomic approach to studying metabolic profiles in rat models with insulin resistance induced by high fructose.

Insulin resistance (IR) is a common risk factor for the development of metabolic diseases, and has gradually become a hot issue for research. It was reported that excessive feeding with high fructose induced insulin resistance in both humans and rats. The aim of this study was to investigate the progression of IR and identify potential biomarkers in urine, plasma and fecal extracts of high fructose-fed rats using a (1)H NMR-based metabonomics approach. The biochemical analysis was also performed. The levels of pyruvate and lactate in the plasma of the IR model rats were reduced significantly, and the levels of citrate and α-ketoglutaric acid (α-KG) in their urine, and the levels of succinate in their feces also decreased, suggesting perturbation of energy metabolism. Decreased levels of taurine in urine and fecal extracts during the whole experiment, together with increased levels of creatine/creatinine in urine, revealed liver and kidney injuries. Decreased levels of choline-containing metabolites in urine and increased levels of betaine in urine and plasma demonstrated altered transmethylation. Changes in hippurate, acetate, propionate and n-butyrate levels suggested disturbance of the intestinal flora in the IR rats. This study indicated that (1)H NMR-based metabonomics can provide biochemical information on the progression of IR and offers a non-invasive means for the discovery of potential biomarkers.

Quercetin inhibits AMPK/TXNIP activation and reduces inflammatory lesions to improve insulin signaling defect in the hypothalamus of high fructose-fed rats

Fructose is a nutritional composition of fruits and honey. Its excess consumption induces insulin resistance-associated metabolic diseases. Hypothalamic insulin signaling plays a pivotal role in controlling whole-body insulin sensitivity and energy homeostasis. Quercetin, a natural flavonoid, has been reported to ameliorate high fructose-induced rat insulin resistance and hyperlipidemia. In this study, we investigated its regulatory effects on the hypothalamus of high fructose-fed rats. Rats were fed 10% fructose in drinking water for 10 weeks. After 4 weeks, these animals were orally treated with quercetin (50 and 100 mg/kg), allopurinol (5 mg/kg) and water daily for the next 6 weeks, respectively. Quercetin effectively restored high fructose-induced hypothalamic insulin signaling defect by up-regulating the phosphorylation of insulin receptor and protein kinase B. Furthermore, quercetin was found to reduce metabolic nutrient sensors adenosine monophosphate-activated protein kinase (AMPK) activation and thioredoxin-interacting protein (TXNIP) overexpression, as well as the glutamine–glutamate cycle dysfunction in the hypothalamus of high fructose-fed rats. Subsequently, it ameliorated high fructose-caused hypothalamic inflammatory lesions in rats by suppressing the activation of hypothalamic nuclear factor κB (NF-κB) pathway and NOD-like receptor 3 (NLRP3) inflammasome with interleukin 1β maturation. Allopurinol had similar effects. These results provide in vivo evidence that quercetin-mediated down-regulation of AMPK/TXNIP and subsequent inhibition of NF-κB pathway/NLRP3 inflammasome activation in the hypothalamus of rats may be associated with the reduction of hypothalamic inflammatory lesions, contributing to the improvement of hypothalamic insulin signaling defect in this model. Thus, quercetin with the central activity may be a therapeutic for high fructose-induced insulin resistance and hyperlipidemia in humans.

Antiproliferation of cardamonin is involved in mTOR on aortic smooth muscle cells in high fructose-induced insulin resistance rats

The objective of this study was to determine possible effects and potential mechanisms of cardamonin on improving insulin resistance and vascular proliferative lesions in the rat's model system. Fed with 60% fructose-enriched diet for 12 weeks, male Sprague–Dawley (SD) rats developed insulin resistance and hyperinsulinemia. They also showed excessive proliferation of the vascular smooth muscle cells (VSMCs) and activation of the mammalian target of rapamycin (mTOR)/translation control proteins p70 ribosomal S6 kinase (P70S6K1)/eukaryotic initiation factor 4E binding protein 1 (4E-BP1) signaling in the rat thoracic aorta. From weeks 9–12, cardamonin was injected into the peritoneal cavity once daily. Under the detection of microscopy and electron microscopy, cardamonin improved hyperinsulinemia and inhibited proliferation of VSMCs in the thoracic aorta of rats in a dose-dependent manner. By the Real-Time RT-PCR, mRNA expression of mTOR, P70S6K1 and 4E-BP1 was significantly reduced in cardamonin treated rats. Similarly, protein over-expression of mTOR and p-P70S6K1 was obviously inhibited by immunohistochemical analyses. These findings suggest that cardamonin may play a role in ameliorating insulin resistance and smooth muscle hyperplasia of major vessels in fructose-induced rats, possibly via a mechanism that involves the modulation of insulin/mTOR signaling.