Effect of nano yam polysaccharide on the blood glucose and blood lipid in rats.

Chinese yam is the dry rhizome of dioscoreaceae plant. Polysaccharide in yam is one of significant functional components, its pharmacological effects include glucose-lowering, lipid-lowering, anti-tumor, anti-oxidation and enhancing the immune. The effects of nano yam polysaccharide on the metabolism of blood glucose and blood lipid in model rats were systematically investigated in this study. The results showed that the diabetic rat model can been successfully induced by the peritoneal injection of 200mg/kg alloxan. The rats were fed with the high-fat diet for 30d, which could induce a model of hyperlipidemia rat successfully. After the model rats were fed with nano yam polysaccharide of 50mg/ml and 100mg/ml per day for 12d and 30d, respectively. For each nano yam polysaccharide group, the blood glucose level was significantly reduced, the glucose tolerance, glycogen and the content of C-peptide were improved in alloxan rats. Moreover, the symptom of one little and three more in diabetic rats was ameliorated and the contents of TC, TG and LDL-C in the serum for the high fat rats were significantly decreased.

Relationship between genetic variation at PPP1R3B and levels of liver glycogen and triglyceride.

Genetic variation at rs4240624 on chromosome 8 is associated with an attenuated signal on hepatic computerized tomography, which has been attributed to changes in hepatic fat. The closest coding gene to rs4240624, PPP1R3B, encodes a protein that promotes hepatic glycogen synthesis. Here, we performed studies to determine whether the x-ray attenuation associated with rs4240624 is due to differences in hepatic glycogen or hepatic triglyceride content (HTGC). A sequence variant in complete linkage disequilibrium with rs4240624, rs4841132, was genotyped in the Dallas Heart Study (DHS), the Dallas Liver Study, and the Copenhagen Cohort (n = 112,428) of whom 1,539 had nonviral liver disease. The minor A-allele of rs4841132 was associated with increased hepatic x-ray attenuation (n = 1,572; P = 4 × 10-5 ), but not with HTGC (n = 2,674; P = 0.58). Rs4841132-A was associated with modest, but significant, elevations in serum alanine aminotransferase (ALT) in the Copenhagen Cohort (P = 3 × 10-4 ) and the DHS (P = 0.004), and with odds ratios for liver disease of 1.13 (95% CI, 0.97-1.31) and 1.23 (1.01-1.51), respectively. Mice lacking protein phosphatase 1 regulatory subunit 3B (PPP1R3B) were deficient in hepatic glycogen, whereas HTGC was unchanged. Hepatic overexpression of PPP1R3B caused accumulation of hepatic glycogen and elevated plasma levels of ALT, but did not change HTGC. CONCLUSION: These observations are consistent with the notion that the minor allele of rs4841132 promotes a mild form of hepatic glycogenosis that is associated with hepatic injury. (Hepatology 2018;67:2182-2195).

Effects of Sideritis scardica Extract on Glucose Tolerance, Triglyceride Levels and Markers of Oxidative Stress in Ovariectomized Rats.

Menopause is characterized by deep metabolic disturbances, including decreased insulin sensitivity, adiposity, and changes in lipid profiles. Estrogen replacement therapy can partially reverse these changes, and while it is safe in most healthy postmenopausal women, there are still existing concerns regarding an increased risk for breast and endometrial cancer as well as a risk for cardiovascular and thromboembolic disease. Therefore, certain natural compounds with positive metabolic effects may be considered as a possible alternative or adjunctive treatment in patients not willing to take estrogens or patients with contraindications for estrogens. The aim of this study was to investigate the influence of Sideritis scardica (mountain tea) extract on metabolic disturbances induced by ovariectomy in rats. The study included 24 rats divided into three groups: ovariectomized rats treated with 200 mg/kg S. scardica extract for 24 weeks (n = 8), ovariectomized non-treated (n = 8), and Sham-operated (n = 8) rats. Food intake, weight gain, body composition, fasting glucose levels, response to oral glucose challenge, liver glycogen content, catalase activity, thiol groups, and malondialdehyde concentrations as well as AMP-activated protein kinase activity in liver cells were studied. Ovariectomized rats treated with S. scardica extract had lower blood triglycerides, reduced fasting glucose levels, as well lower glucose peaks after oral glucose challenge, increased liver glycogen content, and significantly higher catalase activity and thiol group concentration than non-treated ovariectomized rats. The ability of S. scardica extract to attenuate metabolic disturbances associated with ovariectomy was associated with the activation of AMP-activated protein kinase in liver cells.

Resveratrol does not affect leptin while it has regulatory effects on liver glycogen levels in exercised and non-exercised rats.

Resveratrol (RES) is a well-known phytocompound and food component which has antioxidative and multifunctional bioactivities. The present study aims to examine how resveratrol administration affects plasma leptin and liver glycogen levels in rats subjected to an acute swimming exercise bout. The study was carried out on Wistar-Albino type adult male rats, each group include 7 rats. Group 1, Control Group. Group 2, Control Swimming Group: The group fed on a standard diet and subjected to an acute swimming exercise bout for 30 minutes at the end of the study. Group 3, Resveratrol Group: The group fed on a standard diet and given (10 mg/kg) resveratrol in drinking water for four weeks. Group 4, Resveratrol + Swimming Group: The group fed on a standard diet, given (10 mg/kg) resveratrol in drinking water for four weeks and subjected to a 30-minute acute swimming exercise at the end of the study. Plasma leptin levels using ELISA method (ng/l) and liver glycogen levels were determined by using histochemical method (number/0.1 mm2). Four weeks resveratrol administration to exercised and not-exercised rats did not cause a change in plasma leptin levels. Liver glycogen levels were 17.00 ± 3.16; 14.12 ± 2.98; 20.82 ± 1.97; 16.38 ± 1.27 (mean ± sd); respectively in groups 1, 2, 3, 4. Resveratrol administration to rats subjected to a bout of acute swimming exercise produced an effect that prevented the decrease in liver glycogen (p < 0.05). The study highlights that resveratrol supplementation may have regulatory effects on liver glycogen levels in exercised and non-exercised rats.

Visualization of acetaminophen-induced liver injury by time-of-flight secondary ion mass spectrometry.

Time-of-flight secondary ion mass spectrometry (MS) provides secondary ion images that reflect distributions of substances with sub-micrometer spatial resolution. To evaluate the use of time-of-flight secondary ion MS to capture subcellular chemical changes in a tissue specimen, we visualized cellular damage showing a three-zone distribution in mouse liver tissue injured by acetaminophen overdose. First, we selected two types of ion peaks related to the hepatocyte nucleus and cytoplasm using control mouse liver. Acetaminophen-overdosed mouse liver was then classified into three areas using the time-of-flight secondary ion MS image of the two types of peaks, which roughly corresponded to established histopathological features. The ion peaks related to the cytoplasm decreased as the injury became more severe, and their origin was assumed to be mostly glycogen based on comparison with periodic acid-Schiff staining images and reference compound spectra. This indicated that the time-of-flight secondary ion MS image of the acetaminophen-overdosed mouse liver represented the chemical changes mainly corresponding to glycogen depletion on a subcellular scale. In addition, this technique also provided information on lipid species related to the injury. These results suggest that time-of-flight secondary ion MS has potential utility in histopathological applications.

Metabolic and histopathological profile of Rattus norvegicus (Wistar) experimentally infected by Angiostrongylus cantonensis (Chen, 1935).

Eosinophilic meningitis is a disease characterized by increased eosinophils in the cerebrospinal fluid (CSF), which is the most commonly caused by invasion of the central nervous system by helminths, as occurs in Angiostrongylus cantonensis infections. The rodent Rattus norvegicus is the definitive natural host and humans act as accidental hosts and can become infected by eating raw or undercooked snails or food contaminated with infective L3 larvae. Recently in Brazil there have been four cases of eosinophilic meningitis due to ingestion of infected Achatina fulica. To evaluate biochemical and histopathological changes caused by this parasite, R. norvegicus were experimentally infected with 100 L3 larvae of A. cantonensis. After the anesthetic procedure, serum from the rodents was collected from the inferior vena cava for evaluation of the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALKP), gamma-glutamyl transferase (GGT), total protein and its fractions. During the necropsy, the liver was collected and weighed. Then a 1-g fragment was extracted from the major lobe to quantify the hepatic glycogen and fragment remainder was taken from the same lobe and fixed in Milloning's formalin for histopathological examination. Additionally, helminths were collected from the brain and lungs of the rodents. The activities of AST, ALT, ALKP and GGT in the serum and hepatic glycogen increased in response to infection, while the levels of globulin and total protein increased only in the eighth week of infection and there was a reduction in the levels of serum glucose. Albumin and bilirubin concentrations remained stable during the experiment. Infection with A. cantonensis caused metabolic and histopathological changes in the rodents. This study can contribute to a better understanding of the relationship between A. cantonensis and R. norvegicus.

Antioxidant and anti-fatigue activities of egg white peptides prepared by pepsin digestion.

BACKGROUND: Some hydrolyzed peptides derived from food proteins possess antioxidant and anti-fatigue activities. In this study, egg white protein powder (EWPP) was hydrolyzed with pepsin for various times, and four peptide fractions were separated from the hydrolysates by ultrafiltration. The antioxidant activity of the four peptide fractions was determined. The peptide fraction with the strongest antioxidant activity was used to evaluate its anti-fatigue effect and probable mechanisms. RESULTS: The egg white peptides (EWPs) fraction with molecular weight 2-5 kDa (named EWPs2) showed stronger antioxidant activity than the other peptide fractions (P < 0.05). The swimming time to exhaustion of mice administered EWPs2 was longer (P < 0.05) than that of the control group. EWPs2 increased the levels of blood glucose (by 28.4-42.2%), muscle glycogen (by 6.4-10.6%) and liver glycogen (by 10.7-23.8%) and significantly decreased the levels of lactic acid in muscle and urea nitrogen in blood (P < 0.05). CONCLUSION: Among the four peptide fractions, EWPs2 possessed the strongest antioxidant activity and exhibited an anti-fatigue effect. The experimental data could clarify partially the anti-fatigue mechanisms of EWPs and provide an important basis for developing EWPs as safe and natural antioxidants and anti-fatigue agents for wide use.

Priming the cow for lactation by rapeseed supplementation in the dry period.

High-producing dairy cows experience a sudden and significant increase in energy requirements due to the onset of milk production in early lactation. They mobilize body reserves, mainly adipose tissue, resulting in an increased risk of production decline and the development of health disorders. The objective of the present study was to investigate the effects of feeding oilseeds (rapeseed) during the dry period, thereby priming dairy cows for metabolism of body fat in early lactation. Forty-three Holstein dairy cows were used, 14 were primiparous and 29 were multiparous (≥2 nd lactation). In the dry period, 8 wk before expected calving until calving, the cows were fed either a diet with a high content of rapeseed in the total mixed ration (HF) or a standard total mixed ration with a low content of fat (CON). During the first 5 wk after calving, all the cows were fed a standard low fat lactation ration. The treatments were evaluated by performance and metabolic variables in blood and liver. The dry period diet had no effects on body weight and body condition score of the cows during the dry period and in early lactation. The daily yield of milk, protein, and lactose did not differ among treatments. However, the milk fat concentration was lower and the daily milk fat production tended to be lower for the cows fed the HF diet in the dry period compared with the cows fed the CON diet. The plasma content of nonesterified fatty acids, cholesterol, and phospholipids in the dry period was increased in the HF dry period diet compared with the CON diet. The lower plasma concentration of uric acid obtained prepartum for the cows fed the HF diet may indicate a lower rumen microbial protein synthesis. Postpartum, the plasma concentration of ß-hydroxybutyric acid tended to be lower for the cows fed the HF dry period diet. The liver content of triglycerides was lower and the liver content of glycogen was higher in early lactation among the cows fed the HF dry period diet compared with the cows fed the CON diet. Based on liver glycogen, triglyceride content, and blood ß-hydroxybutyric acid concentration, it could be argued that intake of oilseeds during the dry period is a positive strategy for priming dairy cows for fat metabolism in the following early lactation.

Hepatic gene expression involved in glucose and lipid metabolism in transition cows: effects of fat mobilization during early lactation in relation to milk performance and metabolic changes.

Insufficient feed intake during early lactation results in elevated body fat mobilization to meet energy demands for milk production. Hepatic energy metabolism is involved by increasing endogenous glucose production and hepatic glucose output for milk synthesis and by adaptation of postcalving fuel oxidation. Given that cows differ in their degree of fat mobilization around parturition, indicated by variable total liver fat concentration (LFC), the study investigated the influence of peripartum fat mobilization on hepatic gene expression involved in gluconeogenesis, fatty acid oxidation, ketogenesis, and cholesterol synthesis, as well as transcriptional factors referring to energy metabolism. German Holstein cows were grouped according to mean total LFC on d 1, 14, and 28 after parturition as low [<200mg of total fat/g of dry matter (DM); n=10], medium (200-300 mg of total fat/g of DM; n=10), and high (>300 mg of total fat/g of DM; n=7), indicating fat mobilization during early lactation. Cows were fed total mixed rations ad libitum and held under equal conditions. Liver biopsies were taken at d 56 and 15 before and d 1, 14, 28, and 49 after parturition to measure mRNA abundances of pyruvate carboxylase (PC); phosphoenolpyruvate carboxykinase; glucose-6-phosphatase; propionyl-coenzyme A (CoA) carboxylase α; carnitine palmitoyl-transferase 1A (CPT1A); acyl-CoA synthetase, long chain 1 (ASCL1); acyl-CoA dehydrogenase, very long chain; 3-hydroxy-3-methylglutaryl-CoA synthase 1 and 2; sterol regulatory element-binding factor 1; and peroxisome proliferator-activated factor α. Total LFC postpartum differed greatly among cows, and the mRNA abundance of most enzymes and transcription factors changed with time during the experimental period. Abundance of PC mRNA increased at parturition to a greater extent in high- and medium-LFC groups than in the low-LFC group. Significant LFC × time interactions for ACSL1 and CPT1A during the experimental period indicated variable gene expression depending on LFC after parturition. Correlations between hepatic gene expression and performance data and plasma concentrations of metabolites and hormones showed time-specific relations during the transition period. Elevated body fat mobilization during early lactation affected gene expression involved in gluconeogenesis to a greater extent than gene expression involved in lipid metabolism, indicating the dependence of hepatic glucose metabolism on hepatic lipid status and fat mobilization during early lactation.

Antihyperglycemic and antihyperlipidemic activities of ethanolic extract of Zygophyllum album in streptozotocin-induced diabetic mice.

Zygophyllum album has been mentioned in Tunisian system of folk medicine to be of value in the treatment of diabetes mellitus. The present study was designed to investigate the possible antihyperglycemic effects of ethanolic extracts of the whole plant of Z. album on blood glucose, plasma insulin, serum lipids and hepatic glycogen and metabolism enzymes of carbohydrate in streptozotocin (STZ)-induced diabetic mice. Administration of the ethanolic extract from plant (100 and 300 mg/kg body weight) for 14 days resulted in significant reduction in plasma glucose, cholesterol, triglycerides, low-density lipoprotein, very-low-density liprotein, hepatic glucokinase and glycogen in STZ diabetic mice. In addition to that, significant increase in plasma high-density lipoprotein, hepatic phosphofructokinase and glucose-6 phosphate dehydrogenase was observed in STZ diabetic mice. After administration of the ethanolic extract, the increased level of plasma insulin is not significant in diabetic mice. In conclusion, the present results showed that the ethanolic extract of Z. album possesses significant antihyperglycemic and antihyperlipidemic effects in experimental model of diabetes mellitus.

Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism.

Glycogen synthase kinase 3 comprises two isoforms (GSK-3alpha and GSK-3beta) that are implicated in type II diabetes, neurodegeneration, and cancer. GSK-3 activity is elevated in human and rodent models of diabetes, and various GSK-3 inhibitors improve glucose tolerance and insulin sensitivity in rodent models of obesity and diabetes. Here, we report the generation of mice lacking GSK-3alpha. Unlike GSK-3beta mutants, which die before birth, GSK-3alpha knockout (GSK-3alpha KO) animals are viable but display enhanced glucose and insulin sensitivity accompanied by reduced fat mass. Fasted and glucose-stimulated hepatic glycogen content was enhanced in GSK-3alpha KO mice, whereas muscle glycogen was unaltered. Insulin-stimulated protein kinase B (PKB/Akt) and GSK-3beta phosphorylation was higher in GSK-3alpha KO livers compared to wild-type littermates, and IRS-1 expression was markedly increased. We conclude that GSK-3 isoforms exhibit tissue-specific physiological functions and that GSK-3alpha KO mice are insulin sensitive, reinforcing the potential of GSK-3 as a therapeutic target for type II diabetes.

Effects of xylitol on blood glucose, glucose tolerance, serum insulin and lipid profile in a type 2 diabetes model of rats.

BACKGROUND/AIMS: The present study was conducted to examine the antidiabetic effects of xylitol in a type 2 diabetes rat model. METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into 3 groups: normal control (NC), diabetic control (DBC) and xylitol (XYL). Diabetes was induced only in the DBC and XYL animal groups by feeding them a 10% fructose solution for 2 weeks followed by an injection (i.p.) of streptozotocin (40 mg/kg body weight). One week after the streptozotocin injection, the animals with a nonfasting blood glucose level of >300 mg/dl were considered to be diabetic. The XYL group was fed further with a 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. RESULTS: After 5 weeks of intervention, food and fluid intake, body weight, blood glucose, serum fructosamine and most of the serum lipids were significantly decreased, and serum insulin concentration and glucose tolerance ability was significantly increased in the XYL group compared to the DBC group. Liver weight, liver glycogen and serum triglycerides were not influenced by feeding with xylitol. CONCLUSION: The data of this study suggest that xylitol can be used not only as a sugar substitute but also as a supplement to antidiabetic food and other food products.

Liver protein expression in dairy cows with high liver triglycerides in early lactation.

Fatty liver is a frequent subclinical health disorder in dairy cows that may lead to disorders related to the liver function. However, the effect of triglyceride (TG) accumulation on liver metabolic pathways is still unclear. The objective was, therefore, to characterize quantitative differences in the liver proteome between early lactation dairy cows with a low or high liver TG content. The liver proteome analysis indicated that a high liver TG content in early lactation dairy cows is associated with increased oxidation of saturated fatty acids, oxidative stress, and urea synthesis and decreased oxidation of unsaturated fatty acids. Furthermore, liver gluconeogenesis is apparently not impaired by an increased liver TG content. Based on correlations between liver proteins and plasma components, we suggest that future studies investigate the sensitivity and specificity of plasma aspartate aminotransferase, ß-hydroxybutyrate, total bilirubin, total bile acids, and γ-glutamyltransferase for potential use as blood-based biomarkers for early detection of fatty liver in dairy cows. Our study is the first to study the proteome of dairy cows with naturally occurring fatty liver in early lactation.

The Extraction of Liver Glycogen Molecules for Glycogen Structure Determination.

Liver glycogen is a hyperbranched glucose polymer that is involved in the maintenance of blood sugar levels in animals. The properties of glycogen are influenced by its structure. Hence, a suitable extraction method that isolates representative samples of glycogen is crucial to the study of this macromolecule. Compared to other extraction methods, a method that employs a sucrose density gradient centrifugation step can minimize molecular damage. Based on this method, a recent publication describes how the density of the sucrose solution used during centrifugation was varied (30%, 50%, 72.5%) to find the most suitable concentration to extract glycogen particles of a wide variety of sizes, limiting the loss of smaller particles. A 10 min boiling step was introduced to test its ability to denature glycogen degrading enzymes, thus preserving glycogen. The lowest sucrose concentration (30%) and the addition of the boiling step were shown to extract the most representative samples of glycogen.

Adrenal glands are essential for activation of glucogenesis during undernutrition in fetal sheep near term.

In adults, the adrenal glands are essential for the metabolic response to stress, but little is known about their role in fetal metabolism. This study examined the effects of adrenalectomizing fetal sheep on glucose and oxygen metabolism in utero in fed conditions and after maternal fasting for 48 h near term. Fetal adrenalectomy (AX) had little effect on the rates of glucose and oxygen metabolism by the fetus or uteroplacental tissues in fed conditions. Endogenous glucose production was negligible in both AX and intact, sham-operated fetuses in fed conditions. Maternal fasting reduced fetal glucose levels and umbilical glucose uptake in both groups of fetuses to a similar extent but activated glucose production only in the intact fetuses. The lack of fasting-induced glucogenesis in AX fetuses was accompanied by falls in fetal glucose utilization and oxygen consumption not seen in intact controls. The circulating concentrations of cortisol and total catecholamines, and the hepatic glycogen content and activities of key gluconeogenic enzymes, were also less in AX than intact fetuses in fasted animals. Insulin concentrations were also lower in AX than intact fetuses in both nutritional states. Maternal glucose utilization and its distribution between the fetal, uteroplacental, and nonuterine maternal tissues were unaffected by fetal AX in both nutritional states. Ovine fetal adrenal glands, therefore, have little effect on basal rates of fetal glucose and oxygen metabolism but are essential for activating fetal glucogenesis in response to maternal fasting. They may also be involved in regulating insulin sensitivity in utero.

Chronic supplementation with shark liver oil for reducing tumor growth and cachexia in walker 256 tumor-bearing rats.

We investigated the effect of chronic supplementation with shark liver oil (SLO), an antitumor supplement source of n-3 fatty acids and 1-O-alkylglycerols, alone and combined with coconut fat (CF), a source of saturated fatty acids, on Walker 256 tumor growth and cachexia. Male rats were supplemented daily and orally with SLO and/or CF (1 g per kg body weight) for 7 wk. After 7 wk, 50% of animals were subcutaneously inoculated with 3 × 10(7) Walker 256 tumor cells. After 14 days, the rats were killed, the tumors were removed for lipid peroxidation measurement, and blood was collected for glycemia, triacylglycerolemia, and lacticidemia evaluation. Liver samples were obtained for glycogen measurement. Unlike CF, supplementation with SLO promoted gain in body weight, reduction of tumor weight, and maintained glycemia, triacylglycerolemia, lacticidemia, and liver glycogen content to values similar to non-tumor-bearing rats. Combined supplementation of SLO with CF also showed a reversion of cachexia with gain in body mass, reduction of lacticidemia, maintaining the liver glycogen store, and reduction in tumor weight. SLO, alone or combined with CF, promoted increase of tumor lipid peroxidation. In conclusion, SLO supplemented chronically, alone or associated with CF, was able to reduce tumor growth and cachexia.

Protective effects of gallic acid on hepatic lipid peroxide metabolism, glycoprotein components and lipids in streptozotocin-induced type II diabetic Wistar rats.

We evaluated the protective effects of gallic acid (3,4,5-trihydroxybenzoic acid) on hepatic lipid peroxidation products, antioxidants, glycoprotein components, and lipids in streptozotocin-induced type II diabetic rats. To induce type II diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg/kg. Gallic acid (10 and 20 mg/kg) treatment was given to diabetic rats orally using an intragastric tube daily for 21 days. Streptozotocin-induced diabetic rats showed a significant increase in the levels of blood glucose, hepatic lipid peroxidation products, glycoprotein components, lipids, and the activity of HMG-CoA reductase and a significant decrease in the levels of plasma insulin and liver glycogen. In addition to this, the activities/levels of hepatic antioxidants were decreased in diabetic rats. Gallic acid (10 and 20 mg/kg) treatment showed significant protective effects on all the biochemical parameters studied in diabetic rats. Thus, our study shows the antihyperglycemic, antilipid peroxidative, antioxidant, and antilipidemic effects of gallic acid in streptozotocin-induced type II diabetic rats. A diet containing gallic acid may be beneficial to type II diabetic patients.

Effects of Teucrium polium spp. capitatum flavonoids on the lipid and carbohydrate metabolism in rats.

CONTEXT: The main objective of the study was to investigate the biochemical mechanism of the antidiabetic activities of the dry extracts of Teucrium polium L. ssp. capitatum (L.) Arcangeli (Lamiaceae), from Republic of Macedonia, traditionally used to treat diabetes. MATERIALS AND METHODS: Aerial parts of the plant were extracted in alcohol and freeze- or spray-dried, analyzed by high performance liquid chromatography (HPLC) and examined for insulinotropic effect in INS-1E cells in vitro. Their effect on blood glucose, lipids and carbohydrate-related enzymes was tested in normo- and streptozotocin hyperglycemic rats. RESULTS AND DISCUSSION: HPLC analyses revealed several flavonoids: luteolin, apigenin, cirsiliol, diosmetin, cirsimaritin and cirsilineol as both free aglycons and glycosides. The extract and mixture of commercial flavonoids showed a distinct insulinotropic effect on INS-1E cells at 500 µg/ml. Intragastric (i.g.) administration of identical doses of the extract (125 mg/kg) in both normo- and hyperglycemic rats was more efficient in lowering the blood glucose than intraperitoneal injection (35% vs. 24% reduction) with highest effect (50% reduction) 8 h after administration. After 10 days of treatment, the magnitude of the effect was comparable to i.g. administration of 2.5 mg/kg of glibenclamide (38% reduction). No effect was seen on blood lipid profiles. In OGTT (oral glucose tolerance test), the extract lowered blood glucose levels by ~35%. The treatment reduced hepatic glycogen and tended to normalize the activity of gluconeogenic enzymes. CONCLUSION: The results demonstrate that examined plant extracts contain flavonoids with insulinotropic and antihyperglycemic effects.

Ethanol extract of mulberry leaves partially restores the composition of intestinal microbiota and strengthens liver glycogen fragility in type 2 diabetic rats.

BACKGROUND: Mulberry leaf as a traditional Chinese medicine is able to treat obesity, diabetes, and dyslipidemia. It is well known that diabetes leads to intestinal microbiota dysbiosis. It is also recently discovered that liver glycogen structure is impaired in diabetic animals. Since mulberry leaves are able to improve the diabetic conditions through reducing blood glucose level, it would be interesting to investigate whether they have any positive effects on intestinal microbiota and liver glycogen structure. METHODS: In this study, we first determined the bioactive components of ethanol extract of mulberry leaves via high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS). Murine animal models were divided into three groups, normal Sprague-Dawley (SD) rats, high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic rats, and HFD/STZ-induced rats administered with ethanol extract of mulberry leaves (200 mg/kg/day). Composition of intestinal microbiota was analyzed via metagenomics by sequencing the V3-V4 region of 16S rDNAs. Liver glycogen structure was characterized through size exclusion chromatography (SEC). Both Student's t-test and Tukey's test were used for statistical analysis. RESULTS: A group of type 2 diabetic rat models were successfully established. Intestinal microbiota analysis showed that ethanol extract of mulberry leaves could partially change intestinal microbiota back to normal conditions. In addition, liver glycogen was restored from fragile state to stable state through administration of ethanol extract of mulberry leaves. CONCLUSIONS: This study confirms that the ethanol extract of mulberry leaves (MLE) ameliorates intestinal microbiota dysbiosis and strengthens liver glycogen fragility in diabetic rats. These finding can be helpful in discovering the novel therapeutic targets with the help of further investigations.

Cardiomyopathy and exercise intolerance in muscle glycogen storage disease 0.

Storage of glycogen is essential for glucose homeostasis and for energy supply during bursts of activity and sustained muscle work. We describe three siblings with profound muscle and heart glycogen deficiency caused by a homozygous stop mutation (R462-->ter) in the muscle glycogen synthase gene. The oldest brother died from sudden cardiac arrest at the age of 10.5 years. Two years later, an 11-year-old brother showed muscle fatigability, hypertrophic cardiomyopathy, and an abnormal heart rate and blood pressure while exercising; a 2-year-old sister had no symptoms. In muscle-biopsy specimens obtained from the two younger siblings, there was lack of glycogen, predominance of oxidative fibers, and mitochondrial proliferation. Glucose tolerance was normal.