Hepatic Glycogen Research Articles

Peptide Hydrolysate of Telfairia occidentalis Hook f. Seed Protein Promotes Effective Glucose Homeostasis by Improving β-cell Dysfunction and Abating Carbohydrate Metabolic Disturbance in Diabetic Rats

Rising concerns with the use of synthetic antidiabetic drugs have promoted a shift towards the use of natural products. This study therefore investigated the antidiabetic activity of peptide hydrolysate of Telfairia occidentalis (T. occidentalis) seed protein (PHTOSP) in streptozotocin-induced diabetic rats. Thirty-six (36) experimental animals were randomly distributed into six groups (A–F) of six rats each (n = 6). Group A served as normal control while groups B, C, D, E, and F were treated with streptozotocin (STZ, 50 mg/kg body weight, b.w, i.p) dissolved in cold citrate buffer (0.1 M, pH 4.5) to induce type 2 diabetes. Groups C, D, and E were administered 50, 100, and 150 mg/kg b.w PHTOSP, respectively, while groups B and F were diabetic untreated and 5 mg/kg b.w glibenclamide-treated controls, respectively, in the experiment that lasted for 21 days. Subsequently, the analysis of biochemical parameters demonstrated a significant (p<0.05) increase in serum insulin, hepatic glycogen, hexokinase, and glucose-6-phosphate dehydrogenase activities, accompanied by a significant (p<0.05) reduction in fasting serum glucose, glucose-6-phosphatase, and fructose-1,6-bisphosphatase, along with an enhancement in relative body weight. Similarly, PHTOSP demonstrated a significant (p<0.05) improvement on high-density (HDL) and low-density (LDL) lipoproteins, triglyceride (TG), total cholesterol (TC), and atherogenic index (AI) significantly (p<0.05). In addition, histoarchitectural analysis revealed a reversal of congestion and proliferation of inflammatory cells in the pancreatic tissue following treatment with PHTOSP. Therefore, PHTOSP might possess potential antidiabetic properties such that it improves glycolytic pathway and promotes cell survival that are helpful in the management of diabetes mellitus (DM).

Structural characterization of Hericium erinaceus polysaccharides and the mechanism of anti-T2DM by modulating the gut microbiota and metabolites

A low molecular weight polysaccharides of HEP-1, with molecular weights of 1.67 × 104 Da and composition of →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, β-D-Glcp-(1→ and →3,6)-β-D-Glcp-(1→, was isolated and characterized from the fruiting body of Hericium erinaceus. The results indicated that HEP-1 showed potential effects against T2DM-induced imbalance of glucose and lipid metabolism by promoting the serum glucose uptake by hepatic glycogen synthesis via activating the IRS/PI3K/AKT signaling pathway, and inhibiting fatty acid synthesis and reducing hepatic lipid accumulation via activating the AMPK/SREBP-1c signaling pathways. Besides, HEP-1 promoted the production of beneficial bacteria in the gut, and increased the beneficial metabolites in liver through the gut-liver axis, consequently, resisting the occurrence of T2DM.

(m-CF3-PhSe)2 counteracts metabolic disturbances and hypothalamic inflammation in a lifestyle rodent model.

An unhealthy lifestyle is associated with metabolic disorders and neuroinflammation. In this study, the efficacy of m-trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2] against lifestyle model-related metabolic disturbances and hypothalamic inflammation in young mice was investigated. From postnatal day 25 (PND25) to 66, male Swiss mice were subjected to a lifestyle model, an energy-dense diet (20:20% lard: corn syrup) and sporadic ethanol (3x/week). Ethanol was administrated intragastrically (i.g., 2g/kg) to mice from PND45 to 60. From PND60 to 66, mice received (m-CF3-PhSe)2 (5mg/kg/day; i. g). (m-CF3-PhSe)2 reduced relative abdominal adipose tissue weight, hyperglycemia, and dyslipidemia in mice exposed to the lifestyle-induced model. (m-CF3-PhSe)2 normalized hepatic cholesterol and triglyceride levels, and the activity of G-6-Pase increased in lifestyle-exposed mice. (m-CF3-PhSe)2 was effective in modulating hepatic glycogen levels, citrate synthase and hexokinase activities, protein levels of GLUT-2, p-IRS/IRS, p-AKT/AKT, redox homeostasis, and inflammatory profile of mice exposed to a lifestyle model. (m-CF3-PhSe)2 counteracted hypothalamic inflammation and the ghrelin receptor levels in mice exposed to the lifestyle model. (m-CF3-PhSe)2 reversed the decreased levels of GLUT-3, p-IRS/IRS, and the leptin receptor in the hypothalamus of lifestyle-exposed mice. In conclusion, (m-CF3-PhSe)2 counteracted metabolic disturbances and hypothalamic inflammation in young mice exposed to a lifestyle model.

Accelerated Wound Healing in Diabetic Rat by miRNA-185-5p and Its Anti-Inflammatory Activity.

Addressing both inflammation and epithelialization during the treatment of diabetic foot ulcers is an important step, but current treatment options are limited. MiRNA has important prospects in the treatment of diabetic foot refractory wound ulcers. Previous studies have reported that miR-185-5p reduces hepatic glycogen production and fasting blood glucose levels. We herein hypothesized that miR-185-5p might play an important role in the field of diabetic foot wounds. MiR-185-5p in skin tissue samples from patients with diabetic ulcers and diabetic rats were measured using quantitative real-time PCR (qRT-PCR). The streptozotocin-induced diabetes rat model (male Sprague-Dawley rats) for diabetic wound healing was conducted. The therapeutic potential was observed by subcutaneous injection of miR-185-5p mimic into diabetic rat wounds. The anti-inflammation roles of miR-185-5p on human dermal fibroblast cells were analyzed. We found that miR-185-5p is significantly downregulated in diabetic skin (people with DFU and diabetic rats) compared to controls. Further, in vitro upregulation of miR-185-5p decreased the inflammatory factors (IL-6, TNF-α) and intercellular adhesion molecule 1 (ICAM-1) of human skin fibroblasts under advanced glycation end products (AGEs). Meanwhile, the increase of miR-185-5p promoted cell migration. Our results also confirmed that the topical increase of miR-185-5p decreases diabetic wound p-nuclear factor-κB (p-NF-κB), ICAM-1, IL-6, TNF-α, and CD68 expression in diabetic wounds. MiR-185-5p overexpression boosted re-epithelization and expedited wound closure of diabetic rats. MiR-185-5p accelerated wound healing of diabetic rats, reepithelization, and inhibited the inflammation of diabetic wounds in the healing process, a potentially new and valid treatment for refractory diabetic foot ulcers.

Hibiscus sabdariffa on Fibroblast Growth Factor 21 (FGF21) on Diabetes Mellitus Type 2 Patients

FGF21 has a role in modulating the uptake of macronutrients in the body. It is produced by the liver in response to high carbohydrate intake and acts as a signal to the brain to reduce carbohydrate intake. Liver is the main site for FGF21 production under the regulation of Unfolding Protein Response (UPR) in hepatocytes. FGF21 has an important role in regulating peripheral glucose tolerance as well as lipid metabolism. FGF21 expression in the liver depends on the PKR-like ER kinase (PERK)–eukaryotic initiation factor 2? (eIF2?)–activating transcription factor 4 (ATF4) pathway. FGF21 can regulate the expression of glucose transporter 1, and increase glucose uptake. In addition, research shows that FGF21 can reduce blood sugar levels and also body weight in mice1. FGF21 can also increase insulin sensitivity by suppressing hepatic glucose production and increasing hepatic glycogen content, so that this can improve systemic glucose intolerance and insulin resistance. The researchers attempted to discover the influence of Hibiscus sadariffa on FGF21 on Diabetes mellitus type 2 patients. The method used was literature review with data generated from various sources such as Google Scholar, Scopus, and Pubmed. FGF21 has an effect on the function of ? and ß cells in the pancreas organ. In the islets of the pancreatic organs of rats with DM, administration of FGF21 increased insulin levels, induced insulin secretion, and inhibited glucagon secretion.

A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per- and polyfluoroalkyl substances and relevance to human health.

Some per- and poly-fluoroalkyl substances (PFAS) cause neonatal mortality and lower birth weight in rodents. We constructed an Adverse Outcome Pathway (AOP) network for neonatal mortality and lower birth weight in rodents, comprising three putative AOPs. We then assessed strengths of the evidence for the AOPs and applicability to PFAS. Finally, we considered the relevance of this AOP network to human health. Literature searches targeted PFAS, peroxisome proliferator-activated receptor (PPAR) agonists, other nuclear receptors, relevant tissues, and developmental targets. We used reviews of established biology and described results of studies with prenatal PFAS exposure that assessed birth weight and neonatal survival. Molecular initiating events (MIEs) and key events (KEs) were proposed and strengths of KE relationships (KERs), applicability to PFAS, and human relevance were assessed. Neonatal mortality has been observed in rodents following gestational exposure to most longer chain PFAS studied, often coincident with lower birth weight. In AOP 1, PPARα activation and PPARγ activation or downregulation are MIEs; placental insufficiency, fetal nutrient restriction, neonatal hepatic glycogen deficit, and hypoglycemia are KEs leading to neonatal mortality and lower birth weight. In AOP 2, constitutive androstane receptor (CAR) and pregnane X receptor (PXR) activation upregulates Phase II metabolism, lowering maternal circulating thyroid hormones. In AOP 3, disrupted pulmonary surfactant function and PPARγ downregulation cause neonatal airway collapse and mortality from respiratory failure. It is likely that different components of this AOP network will apply to different PFAS, largely determined by which nuclear receptors they activate. The MIEs and KEs in this AOP network can occur in humans, but differences in PPAR structure and function, and the timeline of liver and lung development, suggest that humans may be less susceptible to this AOP network. This putative AOP network elucidates knowledge gaps and research needed to better understand the developmental toxicity of PFAS.

ESTIMATION OF AMOUNT OF GLYCOGEN IN HUMAN LIVER THROUGH HISTOMORPHOMETRY UTILIZING IMAGE J IN PAS STAINED SLIDES

Hepatic glycogen is the main buffer for blood glucose levels. Following a meal, hepatocytes take up glucose from the portal vein and store it as glycogen, a branched polymer of glucose residues. Hepatic glycogen content varies 2 fold during the day and can constitute up to 10% of the weight of the liver in humans. During periods of fasting and increased energy demands, hepatic glycogen can be broken down into glucose, which is released into the circulation to maintain blood glucose levels.Histomorphometry is a digital image analysis approach that relies on the identification and analysis of morphological elements in a histological section. It is a technique used for diagnosis of neoplasms and to aid in tailoring cancer treatment.ImageJ is an essential tool for us that fulfills most of our routine image processing and analysis requirements. The near-comprehensive range of import filters that allow easy access to image and meta-data, a broad suite processing and analysis routine, and enthusiastic support from a friendly mailing list are invaluable for all microscopy labs and facilities-not just those on a budget.

Hepatic glycogenolysis and hypometabolism induced by chemogenetic stimulation of C1 neurons.

The precise regulation of blood glucose levels is indispensable for maintaining physiological functions. C1 neurons determine the outflow of the autonomic nervous and endocrine systems to maintain blood glucose levels in the body. In contrast, activation of C1 neurons induces a decrease in activity, suggesting that hypoactivity also participates in maintaining blood glucose levels. To examine this, we evaluated both glycogenolysis and hypometabolism induced by the selective activation of C1 neurons. We used DbhCre/0 mice expressing receptors for chemogenetic tools in C1 neurons, owing to microinjection of the viral vector. C1 neurons were activated by intraperitoneal injection of clozapine N-oxide (CNO). The chemogenetic activation of C1 neurons significantly decreased body temperature, oxygen consumption, and carbon dioxide production. On the other hand, the blood glucose level was increased by the activation of C1 neurons 2 h after CNO administration, even in the fasting state. In this situation, an increase in glucagon and corticosterone levels was observed, while hepatic glycogen content decreased significantly. Plasma insulin level was not changed by the activation of C1 neurons despite the blood glucose level increased. Furthermore, adrenal sympathetic nerve activity was significantly increased by the activation of C1 neurons, and plasma catecholamine levels increased significantly. In conclusion, the selective activation of C1 neurons using chemogenetic tools induced an increase in blood glucose level, probably because of hepatic glycogenolysis and hypometabolism. KEY POINTS: Chemogenetic activation of C1 neurons in medulla oblongata decreased body temperature. Oxygen consumption and carbon dioxide production were decreased by chemogenetic activation of C1 neurons in medulla oblongata. Blood glucose level was increased by chemogenetic activation of C1 neurons in medulla oblongata. Chemogenetic activation of C1 neurons in medulla oblongata increased glucagon, corticosterone, and catecholamine levels in plasma. Increase in blood glucose level by activation of C1 neurons occurred due to combined effect of hepatic glycogenolysis and hypometabolism. Abstract figure legend We investigated the effects of selectively activating C1 neurons using chemogenetic tools on blood glucose levels. The activation of C1 neurons resulted in an increase in blood glucose levels. This increase is due to the activation of hepatic glycogenolysis through the release of humoral factors, including adrenaline, glucagon, and corticosterone. Additionally, the decrease in energy expenditure, as evidenced by a reduction in body temperature, oxygen consumption, and carbon dioxide production, suggests that activation of C1 neurons may induce hypometabolism, which could also contribute to an increase in blood glucose levels. These responses indicate that C1 neurons may serve as a switch for energy conservation to maintain blood glucose levels, presumably by being activated in a stressful situation. This article is protected by copyright. All rights reserved.

Numerical model of hepatic glycogen phosphorylase regulation by nonlinear interdependent dynamics of calcium and $$IP_{3}$$

Numerical model of hepatic glycogen phosphorylase regulation by nonlinear interdependent dynamics of calcium and $$IP_{3}$$

The 15-hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates abnormal hepatic glucose metabolism through PGE2–EP4 receptor–AKT signaling in a type 2 diabetes mellitus mouse model

Type 2 diabetes mellitus (T2DM) is associated with high rates of morbidity and mortality worldwide. Prostaglandin E2 (PGE2) is a lipid signaling molecule that can ameliorate the symptoms of some metabolic diseases, including T2DM, and improve tissue repair and regeneration. Although SW033291 can increase PGE2 levels through its action as a small molecule inhibitor of the PGE2-degrading enzyme 15-hydroxyprostaglandin dehydrogenase, its effects on T2DM remain unclear. In the present study, we evaluated whether SW033291 treatment exerts a protective effect against T2DM and explored the underlying mechanisms. A T2DM mouse model was established using a high-fat diet combined with streptozotocin treatment. Palmitic acid-treated LO2 cells were used as an insulin-resistant cell model. SW033291 treatment reduced body weight and fasting blood glucose levels as well as serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels in vivo. In addition to ameliorating glucose and insulin tolerance, SW033291 treatment reversed the T2DM-induced decrease in glycogen synthesis and increase in gluconeogenesis in the liver. Furthermore, SW033291 administration increased hepatic glycogen synthase kinase 3 beta (GSK3β) phosphorylation levels to promote glycogen synthesis. SW033291 treatment also inhibited gluconeogenesis by upregulating AKT serine/threonine kinase (AKT) and forkhead box O1 (FOXO1) phosphorylation and reducing glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 expression in the livers of T2DM model mice. Additionally, SW033291 treatment improved abnormal hepatic glucose metabolism through the PGE2–EP4 receptor–AKT–GSK3β/FOXO1 signaling pathway in vitro. These results suggest a novel role of SW033291 in improving T2DM and support its potential as a novel therapeutic agent.

A biochemical, theoretical and immunohistochemical study comparing the therapeutic efficacy of curcumin and taurine on T-2 toxin induced hepatotoxicity in rats.

Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity. Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1mg/kg) for 2months, followed by curcumin (80mg/kg) and taurine (50mg/kg) for 3weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done. Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin's therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin's higher binding affinity than taurine. Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.

Antidiabetic Effect of Chinese yam (Dioscorea opposita Thunb.) in High‐Fat Diet/Streptozotocin‐Induced Diabetic Rats

AbstractThis study aims to assess the effect of different doses of Chinese yam (CY) on a high‐fat diet (HFD) and a streptozotocin‐induced diabetic rat model, using resistant starch (RS) as a positive control. Rats in the normal control and diabetes model (DM) groups are fed the standard diet and HFD, respectively. The RS and CY‐intervention groups are fed with a special HFD, in which starch, maltodextrin, and sucrose in the HFD are replaced completely with RS or CY powder in different proportions: 33.33% (1/3), 66.67% (2/3), and 100% respectively. The results show that CY powder can decrease serum levels of total triglycerides, total cholesterol, low‐density lipoprotein cholesterol, fasting blood glucose, and glycated hemoglobin, lower abdominal fat weight and abdominal fat index, increase levels of insulin and hepatic glycogen, and improve glucose tolerance and insulin sensitivity in diabetic rats. In addition, CY reduces oxidative stress and inflammation and reduces spleen weight and spleen index in diabetic rats. Notably, CY shows higher efficacy than RS in glucose tolerance and serum insulin and nitric oxide levels. This study suggests that CY powder may replace RS as a functional food in diabetic diets.

The ameliorative effect of zinc acetate with caffeic acid in the animal model of type 2 diabetes

Recently the complexation-mediated antioxidative and glycaemic control synergism between zinc(II) and caffeic acid was demonstrated in vitro. The present study evaluated the complexation-mediated antidiabetic and antioxidative synergism between zinc(II) and caffeic acid in diabetic rats and the possible underlying mechanisms. Male SD rats were induced with diabetes using 10% fructose and 40 mg/kg bw streptozotocin. The diabetic rats were treated with Zn(II)-caffeic acid complex and its precursors (caffeic acid and zinc acetate) for 4 weeks at predetermined doses. The effect of the treatments on diabetes and oxidative stress was measured. The complex ameliorated diabetic alterations. It reduced polyphagia and polydipsia and recovered weight loss. It increased insulin secretion, insulin sensitivity, hepatic and muscle glycogen, muscle hexokinase activity and Akt phosphorylation, which resulted in improved glucose tolerance and reduced blood glucose in the diabetic rats. The complex concomitantly reduced systemic and tissue lipid peroxidation and increased antioxidant enzymes activity in the diabetic rats. The complex outperformed the antidiabetic and antioxidative action of its precursors and had a broader bioactivity profile. Complexing zinc acetate with caffeic acid improved their ameliorative effect on insulin resistance by ∼24% and 42%, respectively, as well as their anti-hyperglycaemic action by ∼24 – 36% and ∼42 – 47%, respectively, suggesting a complexation-mediated synergism. In some instances, the antidiabetic action of the complex was comparable to metformin, while its antioxidant effect was better than that of metformin. Zinc(II)-caffeic acid complexation may be an alternative approach to improving the efficacy of antidiabetic and antioxidative therapy with minimal adverse or side effects.

The dietary regulation of LEAP2 depends on meal composition in mice.

Ghrelin represents a key hormone regulating energy balance. Upon activation of the growth hormone secretagogue receptor (GHSR), ghrelin increases blood glucose levels, food intake, and promotes weight gain. The liver-expressed antimicrobial peptide 2 (LEAP2) acts as an endogenous antagonist of the GHSR. While the regulation of LEAP2 and its effect on the GHSR likely occur in an opposite pattern to that of ghrelin, the dietary regulation of LEAP2 remains to be described. We, therefore, examined the regulation of LEAP2 by different acute meal challenges (glucose, mixed meal, olive, lard, and fish oil) and diets (chow vs. high-fat) in C57BL/6 male mice. In addition, the effect of specific fatty acids (oleic, docosahexaenoic, and linoleic acid) on LEAP2 was assessed in murine intestinal organoids. While only mixed meal increased liver Leap2 expression, all meal challenges except fish oil increased jejunal Leap2 expression compared to water. Leap2 expression correlated with levels of hepatic glycogen and jejunal lipids. Lipid versus water dosing increased LEAP2 levels in the systemic circulation and portal vein where fish oil was associated with the smallest increase. In line with this, oleic acid, but not docosahexaenoic acid increased Leap2 expression in intestinal organoids. Feeding mice with high-fat versus chow diet not only increased plasma LEAP2 levels, but also the increment in plasma LEAP2 upon dosing with olive oil versus water. Taken together, these results show that LEAP2 is regulated by meal ingestion in both the small intestine and the liver according to the meal/diet of interest and local energy stores.

Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration.

Metabolic diseases are a worldwide health problem. Insulin resistance (IR) is their distinctive hallmark. For their study, animal models that provide reliable information are necessary, permitting the analysis of the cluster of abnormalities that conform to it, its progression, and time-dependent molecular modifications. We aimed to develop an IR model by exogenous insulin administration. The effective dose of insulin glargine to generate hyperinsulinemia but without hypoglycemia was established. Then, two groups (control and insulin) of male Wistar rats of 100 g weight were formed. The selected dose (4 U/kg) was administered for 15, 30, 45, and 60 days. Zoometry, a glucose tolerance test, insulin response, IR, and the serum lipid profile were assessed. We evaluated insulin signaling, glycogenesis and lipogenesis, redox balance, and inflammation in the liver. Results showed an impairment of glucose tolerance, dyslipidemia, hyperinsulinemia, and peripheral and time-dependent selective IR. At the hepatic level, insulin signaling was impaired, resulting in reduced hepatic glycogen levels and triglyceride accumulation, an increase in the ROS level with MAPK-ERK1/2 response, and mild pro-oxidative microenvironmental sustained by MT, GSH, and GR activity. Hepatic IR coincides with additions in MAPK-p38, NF-κB, and zoometric changes. In conclusion, daily insulin glargine administration generated a progressive IR model. At the hepatic level, the IR was combined with oxidative conditions but without inflammation.

MiR-27b-5p regulates chicken liver disease via targeting IRS2 to suppress the PI3K/AKT signal pathway

The liver is a vital organ in chickens that performs a number of crucial physiological functions, including the storage of hepatic glycogen, protein synthesis, detoxification, and deoxidation. The growth and metabolism of the liver are complex processes influenced by factors such as environment, diet, and genetics. MicroRNAs (miRNAs), as post-transcriptional regulatory molecules, play a role in various biological processes. There is growing evidence that miR-27b-5p plays a key role in the regulation of liver development and metabolism in various species. However, its role in chicken livers has yet to be determined. In our experiment, we found that chickens with fatty livers had significantly higher levels of serum triglyceride (TG) and total cholesterol (TC) compared to the normal chickens, while the control group had significantly higher levels of very low-density lipoprotein (VLDL) and serum hormones. Further research showed that the mRNA of miR-27b-5p was highly expressed in fatty livers. By exploring the function of miR-27b-5p in chicken livers, we discovered that it promotes lipogenesis, oxidative stress, and inflammatory responses, leading to hepatocyte apoptosis. Our study also established the mechanism by which miR-27b-5p interacts with its target gene, and found that miR-27b-5p targets insulin receptor substrate 2 (IRS2) and modulates the PI3K/AKT signaling pathway. Additionally, our investigation of IRS2 in chicken hepatocytes revealed that knocking down IRS2 has the same effects as overexpressing miR-27b-5p. In conclusion, our study revealed that miR-27b-5p directly binds to IRS2, inhibiting the PI3K/AKT signaling pathway and causing steatosis, oxidative stress, inflammation, and apoptosis in chicken liver.

Gut microbiome-mediated glucose and lipid metabolism mechanism of star apple leaf polyphenol-enriched fraction on metabolic syndrome in diabetic mice

BackgroundDiabetes is a kind of metabolic syndrome (MetS) that seriously threatens human health globally. The leaf of star apple (Chrysophyllum cainito L.) is an incompletely explored folk medicine on diabetes. And, the effects and mechanisms on diabetes complicated glycolipid metabolism disorders are unknown till now. PurposeThis study aimed to investigate the constituents of star apple leaf polyphenol enriched-fraction (SAP), and elucidate their treatment effects and mechanism on diabetes and accompanied other MetS. MethodsThe components of SAP were tentatively identified by HPLC-Q-TOF-MS/MS. The antioxidant activity was determined by the scavenging of free radicals and hypoglycemic activities by inhibition of α-glucosidase in vitro. HepG2 cells were used for evaluating the alleviation effects of SAP on lipid accumulation. Streptozotocin and high-fat diet induced diabetic mice were grouped to evaluate the effects of different dosages of SAP. 16S rRNA was conducted to analysis gut microbiome-mediated glucose and lipid metabolism mechanism. ResultsIt showed that myricitrin was one of the main active constituents of SAP. SAP not only showed low IC50 on -glucosidase (24.427± 0.626 μg/mL), OH·(3.680± 0.054 μg/mL) and ABTS· (9.155±0.234 μg/mL), but significantly induced the lipid accumulation in HepG2 cells (p < 0.05). SAP at 200 mg/kg·day significantly decreased the blood glucose, insulin and oral glucose tolerance test value (p < 0.05). The insulin resistance indexes and oxidative stress were alleviated after administration. SAP not only attenuated hepatic lipid deposition, but also reversed the hepatic glycogen storage. 16S rRNA sequencing results revealed that the interaction between SAP and gut microbiota led to the positive regulation of beneficial bacteria including Akkermansia, Unspecified S24_7, Alistipes and Unspecified_Ruminococcaceae, which might be one of the mechanisms of SAP on MetS. ConclusionFor the first time, this study explored the regulation effect of star apple leaf polyphenols on the hepatic glycolipid metabolism and studied the underlying mechanism from the view of gut microbiota. These findings indicated that SAP possesses great potential to serve as a complementary medicine for diabetes and associated MetS. It provided scientific evidence for folk complementary medicine on the treatment of diabetes-complicated multiple metabolic disorders.

Antidiabetic and in vitro antioxidant potential of Mormodica charantia L. fruit in Experimentally Induced Wistar Rat Model of Type 2 Diabetes

BACKGROUND: The liver is a vital organ responsible for regulating the normal glucose homeostasis in the body system, and hepatic glucose metabolic dysregulation is one of the most critical elements in the pathogenesis of DM. METHOD: Twenty-five healthy rats aged seven weeks were divided into the following main groups; non-diabetic, diabetic untreated, diabetic treated with 250 mg/kg and 500 mg/kg of MC fruit, and diabetic treated with Metformin (500 mg/kg). Different models of in vitro antioxidant assays of MC fruit were also determined. RESULTS: The results showed that MC fruit has high antioxidant potential against DPPH, hydrogen peroxide, hydroxyl radicals, good reducing ferric power, significant Inhibition of lipid peroxidation and total antioxidant activities. The FBG levels decreased significantly in MC fruit treatment groups compared to diabetes control (DC) rats. The histology of the hepatic tissue of the diabetic untreated rats revealed a marked depletion in glycogen granules and hepatic DNA. These negative features were ameliorated in the MC fruit treated rats, as consistent glycogen granule storage and improved hepatic DNA presence were observed in the MC fruit treated rats. CONCLUSION: MC fruit reduces blood glucose levels in a diabetic rat model, and it also preserves the hepatic DNA and glycogen granules. MC fruit has a significant in vitro antioxidant activity.

Growth-Restricted Fetuses and Offspring Reveal Adverse Sex-Specific Metabolic Responses in Preeclamptic Mice Expressing Human sFLT1.

Fetal adaptations to harmful intrauterine environments due to pregnancy disorders such as preeclampsia (PE) can negatively program the offspring's metabolism, resulting in long-term metabolic changes. PE is characterized by increased circulating levels of sFLT1, placental dysfunction and fetal growth restriction (FGR). Here we examine the consequences of systemic human sFLT1 overexpression in transgenic PE/FGR mice on the offspring's metabolic phenotype. Histological and molecular analyses of fetal and offspring livers as well as examinations of offspring serum hormones were performed. At 18.5 dpc, sFLT1 overexpression resulted in growth-restricted fetuses with a reduced liver weight, combined with reduced hepatic glycogen storage and histological signs of hemorrhages and hepatocyte apoptosis. This was further associated with altered gene expression of the molecules involved in fatty acid and glucose/glycogen metabolism. In most analyzed features males were more affected than females. The postnatal follow-up revealed an increased weight gain of male PE offspring, and increased serum levels of Insulin and Leptin. This was associated with changes in hepatic gene expression regulating fatty acid and glucose metabolism in male PE offspring. To conclude, our results indicate that sFLT1-related PE/FGR in mice leads to altered fetal liver development, which might result in an adverse metabolic pre-programming of the offspring, specifically targeting males. This could be linked to the known sex differences seen in PE pregnancies in human.

Coadministration of olanzapine causes minor impacts on the diabetogenic outcomes induced by dexamethasone treatment in rats

AimsInvestigate whether the coadministration of olanzapine exacerbates the diabetogenic effects of dexamethasone, two agents used in the antiemetic cocktails indicated to mitigate the adverse effects of chemotherapy. Main methodsAdult Wistar rats (both sexes) were treated daily with dexamethasone (1 mg/kg, body mass (b.m.), intraperitoneal (i.p.)) with or without olanzapine (10 mg/kg, b.m., orogastric (o.g.)) for 5 consecutive days. During and at the end of the treatment, we evaluated biometric data and parameters involving glucose and lipid metabolism. Key findingsDexamethasone treatment resulted in glucose and lipid intolerance, higher plasma insulin and triacylglycerol levels, higher content of hepatic glycogen and fat, and higher islet mass in both sexes. These changes were not exacerbated by concomitant treatment with olanzapine. However, coadministration of olanzapine worsened the weight loss and plasma total cholesterol in males, while in females resulted in lethargy, higher plasma total cholesterol, and higher hepatic triacylglycerol release. SignificanceCoadministration of olanzapine does not exacerbate any diabetogenic dexamethasone effect on glucose metabolism and exerts a minor impact on the lipid homeostasis of rats. Our data favor the addition of olanzapine in the antiemetic cocktail considering the low incidence of metabolic adverse effects for the period and dosage analyzed in male and female rats.