Metabolism In Diabetic Rats Research Articles

Semen Cassiae Extract Improves Glucose Metabolism by Promoting GlUT4 Translocation in the Skeletal Muscle of Diabetic Rats.

Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia; its complications lead to disability and even death. Semen Cassiae is a traditional Chinese medicine, which has anti-hypertensive, anti-hyperlipidaemia, anti-oxidation, and anti-ageing properties. Our study was designed to evaluate the action of total anthraquinones of Semen Cassiae extract (SCE) on the improvement of glucose metabolism in diabetic rats and to elucidate the underlying mechanism. First, we evaluated the effect of SCE on normal rats. Next, we observed the effect of SCE using a rat model of diabetes, which was established by feeding rats with high-energy diet for 4 weeks and a single intraperitoneal injection of streptozotocin (STZ; 30 mg/kg) 3 weeks after starting the high-energy diet. Rats in different SCE groups (administered 54, 108, and 324 mg/kg/day of SCE) and metformin group (162 mg/kg/day, positive control drug) were treated with the corresponding drugs 1 week before starting high-energy diet and treatment continued for 5 weeks; meanwhile, rats in the control group were administered the same volume of sodium carboxymethyl cellulose solution (vehicle solution). One week after STZ injection, fasting blood glucose (FBG), oral glucose tolerance (OGT), fasting serum insulin (FSI) and serum lipids were quantified. Finally, the expression of proteins in the phosphatidylinositol-3-kinase (PI3K)–Akt–AS160–glucose transporter isoform 4 (GLUT4) signalling pathway was detected by western blotting. The data indicated that the levels of FBG and serum lipids were significantly lowered, and OGT and FSI were markedly increased in diabetic rats treated with SCE (108 mg/kg/day); however, SCE did not cause hypoglycaemia in normal rats. The molecular mechanisms were explored in the skeletal muscle. SCE markedly restored the decreased translocation of GLUT4 in diabetic rats. Moreover, the protein expressions of phosphorylated-AS160 (Thr642), phosphorylated-Akt (Ser473) and PI3K were significantly increased after SCE treatment in the skeletal muscle. These results indicate that SCE exerts an anti-hyperglycaemic effect by promoting GLUT4 translocation through the activation of the PI3K–Akt–AS160 signalling pathway. Our findings suggest that treatment with SCE, containing anthraquinones, could be an effective approach to enhance diabetes therapy.

Polyphenol-enriched extract of Rosa rugosa Thunb regulates lipid metabolism in diabetic rats by activation of AMPK pathway

This study was designed to investigate the mechanism of polyphenol-enriched extract of Rosa rugosa Thunb (RPE) in the control of dyslipidemia in diabetic rats. RPE was tested at three dosages (37.5 mg/kg, 75 mg/kg and 150 mg/kg) in the rat dyslipidemia model established with high fat diet feeding in combination with STZ injection (30 mg/kg). The RPE effect was evaluated after 4 weeks of treatment. In the RPE-treated rats, hepatic total cholesterol (TC) and triglyceride (TG) were significantly reduced, lipoprotein lipase (LPL) and liver lipase (HL) were significantly increased. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were decreased in the serum. Those effects of RPE were observed primarily at the mediate and high dosages. Expression of FGF21 was increased in the liver tissue and hepatic cell line 1c1c7 by RPE. The signals of p-AMPK, p-ACC, ACC, p-SIRT, and PGC-1α were significantly induced in the liver by RPE. The results suggest that RPE may improve hepatic steatosis and liver function by induction of AMPK signaling activity in the control of dyslipidemia.

Hypoglycemic Mechanism of the Berberine Organic Acid Salt under the Synergistic Effect of Intestinal Flora and Oxidative Stress.

Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.

Vitamin D supplement ameliorates hippocampal metabolism in diabetic rats

Vitamin D deficiency induced by diabetes mellitus is tightly associated with neurodegenerative diseases, but the mechanism is still unknown. Endoplasmic reticulum stress (ER stress) is involved in hippocampal lesion and promote diabetic neuropathy, so we focus on the effects of 1, 25-dihydroxy vitamin D3 on ER stress in hippocampus of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were administrated with different doses of vitamin D and divided into 3 groups: high, low, and blank, compared to wild-type rats which were received the same treatment. At the end of 12 weeks of treatment, the brains of the rats were analyzed by proton magnetic resonance spectroscopy (1H-MRS). Rats were then weighed, tested for blood glucose, serum Ca, P, and vitamin D3, and sacrificed for histopathological analysis of the hippocampus. Neuronal nitric oxide synthase (nNOS) and vitamin D receptor (VDR) expression were measured, as well as ER stress markers, including glucose-regulated protein78 (GRP78), protein kinase-like endoplasmic reticulum kinase (PERK) phosphorylation, eukaryotic initiation factor 2α(eIF-2α) phosphorylation, and CCAAT enhancer-binding protein homologous protein (CHOP). Our study showed that treated with appropriate concentration of active vitamin D could decrease the number of pathological pyramidal neurons, improve hippocampal nerve metabolism, and reduce the over-expression of nNOS, along with the relieved activation of ER stress in hippocampus of diabetic rats. These results suggest that 1,25-dihydroxy vitamin D3 treatment can ameliorate hyperglycemia-induced damage on hippocampal metabolism, possibly through alleviating the aberrant activation of ER stress.

Hypoglycemic and hypolipidemic effect of Vaccinium myrtillus L. leaf and Phaseolus vulgaris L. seed coat extracts in diabetic rats.

The aim of this study was to examine the hypoglycemic and hypolipidemic effects of Vaccinium myrtillus L. leaf (VLE) and Phaseolus vulgaris L. seed coat (PCE) plant extracts, containing polyphenolic compounds, on carbohydrate and lipid metabolism in Wistar rats with streptozotocin (STZ) and high-fructose diet (HFD)-induced diabetes. Male Wistar rats with STZ and HFD-induced diabetes were fed with or without VLE or PCE for 50d. At different intervals, blood glucose and body weight were recorded. Blood samples were used to determine glycated hemoglobin (HbA) and parameters of lipid profile in serum. Additionally, the levels of serum diene conjugates and malondialdehyde were assessed. Results of HbA and blood glucose level analysis showed the ameliorative effect of VLE on carbohydrate metabolism in diabetic rats. Of the eight diabetic animals treated with bilberry leaf extract, four had normal HbA levels. A significant reduction was observed in VLE group in blood glucose level compared with control diabetic rats (level of hyperglycemia decreased to normal values in 50% of animals versus 0% in the control diabetic group). VLE treatment normalized parameters of lipid metabolism. There was no significant difference from the same parameters in the intact control group. Administration of PCE significantly (P<0.05) decreased the levels of plasma triacylglycerol (0.81±0.06mmol/L) and low-density lipoprotein (0.74±0.10mmol/L) in blood serum compared with the diabetic control group (1.36±0.13 and 1.85±0.30, respectively). Moreover, VLE and PLE showed an antioxidant effect on diene compounds in the blood serum of rats. A significant decrease was found in the plasma diene conjugate levels in PLE group (1.16±0.11nmol/mL) compared with control diabetic rats (2.09±0.21nmol/mL; P<0.05). There was no significant difference from the same parameter in the VLE and intact control groups. The set of results that was obtained in the present study reveals lipid-lowering and antioxidant action related to the administration of VLE and PCE in Wistar rats with diabetes, induced by STZ, in combination with a high-carbohydratediet. VLE to a certain extent also reduced hyperglycemia in diabetic animals.

Effects of apelin-13 on myocardium metabolism in diabetic rats

Objectives To investigate the effects of Apelin-13 on myocardial metabolism in diabetic rats. Methods A total of 40 male Wister rats were randomly divided into normal control group (NC, n=8) and experimental group (n=32). Diabetic rats model were induced by high-sugar and high-fat diet combined with low-dose intraperitoneal injection of streptozotocin (STZ). The well-established 28 diabetic model rats were randomly divided into diabetic model group (DM, n=14) and apelin-13 treated group (n=14). In the Apelin-13 group, diabetic rats were administered Apelin-13[0.1 μmol/(kg·d)]by intraperitoneal injection for 10 weeks, while the control group and diabetic model group were given an equal volume of 0.9% NaCl.At the end of the 10th week, all rats were sacrificed after fasting glucose measurement.Levels of serum free fatty acids (FFA) and myocardial FFA were measured by ELISA.Expression of myocardial glucose transporter member 4 (GLUT4) were detected by immunohistochemistry.The mRNA expressions of myocardial PPARα, CD36 and CPT-1 were detected by real-time fluorescence quantitative PCR. Results Fasting blood glucose, serum FFA and myocardial FFA were significantly higher in DM group than in NC group (all P 0.05) in Apelin-13 treated group than in DM group; but serum FFA was not significantly lower(Ρ<0.05). The mRNA expressions of PPARα, CD36, CPT-1 in cardiac myocyte were higher in DM group and Apelin-13 treated group than in control(P<0.05), and lower in Apelin-13 treated group than in DM group(P<0.05). The expression of myocardial GLUT4 was significantly lower in DM group(1.138±0.316)and in Apelin-13-treated group (4.631±1.832)than in NC group(9.132±2.156), (F=65.507, P<0.05), and higher in Apelin-13-treated group than in DM group(P<0.05). Conclusions Apelin-13 increases myocardial expression of GLUT4, improves utilization of FFA, and it can effectively reduce the expression of PPARα, CD36 and CPT-1.Therefore, it may play a vital role in the improvement of myocardial metabolism in diabetic rats. Key words: Apelin-13; Diabetes mellitus; Energy metabolism; Myocardium

Morin activates the Nrf2-ARE pathway and reduces oxidative stress-induced DNA damage in pancreatic beta cells

Oxidative stress is an important factor contributing to the pathogenesis of diabetes and its complications. In our earlier study, we demonstrated the antidiabetic efficacy of morin by regulating key enzymes of carbohydrate metabolism in diabetic rats. The present study was designed to assess the antigenotoxic potential of morin in pancreatic β-cells, using the COMET assay. To explore its potential mechanisms of action, three genotoxic agents, H2O2 which induces DNA damage by the generation of reactive oxygen species, streptozotocin (STZ) by RNS and Methyl methanesulfonate (MMS) by DNA alkylation was used. We found that STZ and H2O2- induced genotoxicity was dose dependently reduced by morin as assessed by DNA tail length, tail moment, DNA content and olive moment. Since the protective property was found to be specific against oxidative DNA damage, we explored the molecular mechanism underlying morin-induced Nuclear factor erythroid 2-related factor 2 (Nrf2) activation in pancreatic β-cells as assessed by ARE-driven downstream target genes with Luciferase reporter assay. In addition, morin inhibited intracellular free radical generation as assessed by using DCFDA and increased the intra cellular antioxidants viz, superoxide dismutase and catalase in INS-1E cells. In addition, morin attenuated glucose-stimulated insulin secretion following exposure to oxidative stress by STZ (P<0.05). Collectively, our data provide evidence that morin protects pancreatic β-cells against oxidative stress-induced DNA damage by activating the Nrf2 signaling pathway

Effect of Aqueous Extract of Phaseolus Vulgaris on the Regulation of Glucose and Lipid Metabolism in Diabetic Rats

Effect of Aqueous Extract of Phaseolus Vulgaris on the Regulation of Glucose and Lipid Metabolism in Diabetic Rats

ALOE-EMODIN GLYCOSIDES AMELIORATE GLUCOSE UTILIZATION VIA INSULIN DOWNSTREAM REGULATORS: AN IN VIVO INVESTIGATION

&lt;p&gt;ABSTRACT&lt;br /&gt;Objective: Aloe-emodin glycosides (AEG) isolated from Cassia fistula stimulates glucose transport and glycogen storage through a phosphatidylinositol&lt;br /&gt;3 kinase (PI3K)-dependent mechanism in L6 myotubes and inhibits adipocytes differentiation in 3T3L1 adipocytes was previously reported. This&lt;br /&gt;study intended to investigate the insulin mimetic effect of AEG by in vivo method.&lt;br /&gt;Methods: Male Wistar albino rats were randomly allocated into two groups and fed for a period of 3-week. The high-fat diet group animals were&lt;br /&gt;injected with a low dose (35 mg/kg) of streptozotocin to induce Type-2 diabetes. The diabetic rats were then treated with low dose: 10 mg/kg and&lt;br /&gt;high dose: 30 mg/kg for a period of 21-day. A dose-dependent decrease in fasting blood glucose, cholesterol, and triglycerides levels on treatment&lt;br /&gt;with AEG. The carbohydrate metabolism in diabetic rats appeared to improve due to regulation in hepatic enzymes such as hexokinase, glucose-6phosphatase,&lt;br /&gt;and fructose&lt;br /&gt;1,6-bisphosphatase with a concomitant increase&lt;br /&gt;in glycogen&lt;br /&gt;content.&lt;br /&gt;Results: AEG decreased lipid peroxidation and improved the antioxidant (enzymatic and nonenzymatic) levels in the liver of diabetic rats. Treatment&lt;br /&gt;with AEG (30 mg/kg) augmented the phosphorylation of insulin downstream regulators such as insulin receptor beta, insulin receptor substrate 1,&lt;br /&gt;PI3K, glucose transporter 4, glycogen synthase kinase 3 beta, and peroxisome proliferator activator receptor gamma in the skeletal muscle tissue of&lt;br /&gt;the Type-2 diabetic rats compared to vehicle-treated diabetic rats.&lt;br /&gt;Conclusion: The present results suggested that AEG could serve as an interesting candidate in the drug development for the management of diabetes.&lt;br /&gt;Keywords: Aloe-emodin glycoside, Type-2 diabetes, High-fat diet/streptozotocin, Carbohydrate Metabolism, Glycogen, Antioxidant enzyme.&lt;/p&gt;

Chronic intermittent hypobaric hypoxia ameliorates diabetic nephropathy through enhancing HIF1 signaling in rats

AimOur previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had anti-diabetes effect. The present study was to explore the renal protective effect of CIHH in diabetic rats. MethodsSprague–Dawley rats were randomly divided into three groups: diabetes mellitus group (DM, induced by high-fat diet combined with low-dose streptozotocin), diabetes plus CIHH treatment group (DM+CIHH, simulated 5000-m altitude, 6h per day for 28days, after diabetes model confirmed) and control group (CON). Systolic arterial blood pressure (SAP), blood biochemicals, urinary albumin, and histopathology of kidney were determined. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, protein levels of hypoxia induced factors (HIFs) and transforming growth factor β1 (TGF-β1) in kidney were assayed. ResultsThe increased SAP, urinary albumin, hyperplasia of glomerular, fibrosis in mesangial and glomerular, and abnormal lipid metabolism in diabetic rats were ameliorated by CIHH treatment. And decreased superoxide dismutase (SOD) activity and increased malondialdehyde (MDA) level in diabetic kidney were reversed in CIHH-treated DM rats. In addition up-regulated TGF-β1 and down-regulated HIF1α in diabetic kidney returned back to normal level in CIHH-treated DM rats. ConclusionsThese data demonstrated for the first time that CIHH had protective effects against the early stage damage of diabetic nephropathy through activating HIF1 signaling, improving anti-oxidation and inhibiting TGF-β1 signaling in diabetic rats.

Anti-diabetic effects of soluble and insoluble dietary fibre from deoiled cumin in low-dose streptozotocin and high glucose-fat diet-induced type 2 diabetic rats

The effects of soluble dietary fibre (SDF) and insoluble dietary fibre (IDF) from deoiled cumin on low-dose streptozotocin and high glucose-fat-induced type 2 diabetes rats were examined. Male Wistar rats were divided into nine groups: control (non-diabetic, no SDF or IDF intake), model (diabetes only), metformin, high-dose SDF (5 g/kg body weight), middle-dose SDF (500 mg/kg body weight), low-dose SDF (250 mg/kg body weight), high-dose IDF (5 g/kg body weight), middle-dose IDF (500 mg/kg body weight), and low-dose IDF (250 mg/kg body weight). SDF treatments, in particular, middle-dose SDF for 4 weeks, induced better regulation of blood glucose, insulin, hormones, and liver lipid metabolism in diabetic rats, accompanied by increased levels of short-chain fatty acids in colon and decreased fatty degeneration of liver. Our results collectively support the therapeutic potential of SDF from deoiled cumin in type 2 diabetes.

Comparative anti-inflammatory and lipid-normalizing effects of metformin and omega-3 fatty acids through modulation of transcription factors in diabetic rats.

BackgroundEmerging evidence suggests beneficial effects of omega-3 fatty acids on diabetic complications. The present study compared the progressive effects of metformin and flax/fish oil on lipid metabolism, inflammatory markers, and liver and renal function test markers in streptozotocin-nicotinamide-induced diabetic rats.MethodsStreptozotocin-induced diabetic rats were randomized into control and four diabetic groups: streptozotocin (STZ), metformin (200 mg/kg body weight (b.w)/day (D)), flax and fish oil (500 mg/kg b.w/D).ResultsMetformin and flax and fish oil exhibited increased expression of transcription factor peroxisome proliferator-activated receptor γ while the treatment downregulated sterol regulatory element-binding protein 1 and nuclear factor kβ as compared to those of the STZ group. Apart from modulation of transcription factor expression, the expression of fatty acid synthase, long chain acyl CoA synthase, and malonyl-CoA-acyl carrier protein transacylase was lowered by flax/fish oil treatment. Serum cholesterol, triglycerides, and VLDL were also significantly reduced in the treatment groups as compared to those in the STZ group. Although pathological abnormalities were seen in the liver and kidneys of rats on metformin, no significant changes in liver/renal function markers were observed at day 15 and day 30 of the treatment groups. Flax/fish oil had protective effects toward pathological abnormalities in the liver and kidney. Flax/fish oil improved lipid profile and alkaline phosphatase at day 30 as compared to that at day 15.ConclusionsThe present study demonstrates potential beneficial effects of metformin and flax/fish oil intervention in improving serum lipid profile by regulating the expression of transcription factors and genes involved in lipid metabolism in diabetic rats. In addition, these interventions also lowered the expression of atherogenic cytokines. The protective effects of flax/fish oil are worth investigating in human subjects on metformin monotherapy.

A 70% Ethanol Extract of Mistletoe Rich in Betulin, Betulinic Acid, and Oleanolic Acid Potentiated β-Cell Function and Mass and Enhanced Hepatic Insulin Sensitivity.

We investigated that the long-term consumption of the water (KME-W) and 70% ethanol (KME-E) mistletoe extracts had antidiabetic activities in partial pancreatectomized (Px) rats. Px rats were provided with a high-fat diet containing 0.6% KME-E, 0.6% KME-W, and 0.6% dextrin (control) for 8 weeks. As normal-control, Sham-operated rats were provided with 0.6% dextrin. In cell-based studies, the effects of its main terpenoids (betulin, betulinic acid, and oleanolic acid) on glucose metabolism were measured. Both KME-W and KME-E decreased epididymal fat mass by increasing fat oxidation in diabetic rats. KME-E but not KME-W exhibited greater potentiation of first-phase insulin secretion than the Px-control in a hyperglycemic clamp. KME-E also made β-cell mass greater than the control by increasing β-cell proliferation and decreasing its apoptosis. In a euglycemic-hyperinsulinemic clamp, whole-body glucose infusion rate and hepatic glucose output increased with potentiating hepatic insulin signaling in the following order: Px-control, KME-W, KME-E, and normal-control. Betulin potentiated insulin-stimulated glucose uptake via increased PPAR-γ activity and insulin signaling in 3T3-L1 adipocytes, whereas oleanolic acid enhanced glucose-stimulated insulin secretion and cell proliferation in insulinoma cells. In conclusion, KME-E prevented the deterioration of glucose metabolism in diabetic rats more effectively than KME-W and KME-E can be a better therapeutic agent for type 2 diabetes than KME-W.

Effects of sleeve gastrectomy with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats.

To explore the effect of sleeve gastrectomy (SG) with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats. Diabetic rats, which were induced by high-fat diet (HFD), nicotinamide and low-dose streptozotocin, underwent sham operations, SG, SG with jejuno-ileal loop (SG-JI) and SG with jejuno-jejunal loop (SG-JJ) followed by postoperative HFD. Then, at the time points of baseline and 2, 12 and 24 wk postoperatively, we determined and compared several variables, including the area under the curve for the results of oral glucose tolerance test (AUCOGTT), serum levels of triglyceride, cholesterol and ghrelin in fasting state, homeostasis model assessment of insulin resistance (HOMA-IR), body weight, calorie intake, glucagon-like peptide (GLP)-1 and insulin secretions after glucose gavage at dose of 1 g/kg. At 2 wk postoperatively, rats that underwent SG, SG-JJ and SG-JI, compared with sham-operated (SHAM) rats, demonstrated lower body weight, calorie intake and ghrelin (P < 0.05 vs SHAM), enhanced secretion of insulin and GLP-1 after glucose gavage (P < 0.05 vs SHAM), improved AUCOGTT, HOMA-IR, fasting serum triglyceride and cholesterol (AUCOGTT: 1616.9 ± 83.2, 837.4 ± 83.7, 874.9 ± 97.2 and 812.6 ± 81.9, P < 0.05 vs SHAM; HOMA-IR: 4.31 ± 0.54, 2.94 ± 0.22, 3.17 ± 0.37 and 3.41 ± 0.22, P < 0.05 vs SHAM; Triglyceride: 2.35 ± 0.17, 1.87 ± 0.23, 1.98 ± 0.30 and 2.04 ± 0.21 mmol/L, P < 0.05 vs SHAM; Cholesterol: 1.84 ± 0.21, 1.53 ± 0.20, 1.52 ± 0.20 and 1.46 ± 0.23 mmol/L). At 12 wk postoperatively, rats receiving SG-JJ and SG-JI had lower body weight, reduced levels of triglyceride and cholesterol and elevated level of GLP-1 compared to those receiving SG (P < 0.05 vs SG). At 24 wk after surgery, compared with SG, the advantage of SG-JJ and SG-JI for glucolipid metabolism was still evident (P < 0.05 vs SG). SG-JI had a better performance in lipid metabolism and GLP-1 secretion of rats than did SG-JJ. SG combined with intestinal loop induces better glycolipid metabolism than simple SG, with the lipid metabolism being more improved with SG-JI compared to SG-JJ.

Effect of hypothalamic-pituitary-adrenal axis alterations on glucose and lipid metabolism in diabetic rats.

This study investigated the relationship between alterations in the hypothalamic-pituitary-adrenal (HPA) axis function and glucose and lipid metabolism in diabetic rats. To accomplish this a diabetes model was established by jointly administering a long-term high-fat diet plus Streptozotocin (STZ; 50 mg/kg ip). The rats were randomly divided into four groups: 1) a normal control group, 2) a model group, 3) astragalus polysaccharide (APS) group, and 4) a metformin group. APS and metformin hydrochloride were administered intragastrically (100 mg∙kg(-1)d(-1)). Rat blood glucose and body weight were measured once per week, and urine was collected for 24 h after 30 days of administration of APS. The levels of blood lipids, insulin, and corticosterone (CORT), as well as hypothalamic CRH, pituitary ACTH, urine sugar and CORT were measured. Compared with the normal control group, the levels of blood sugar, urine sugar, TC, and TG significantly increased in the model group, and the levels of hepatic glycogen and HDL-C decreased. Administration of APS was shown to reverse these changes. Furthermore, as compared with the normal control group, the levels of insulin and hypothalamic CRH in the model group decreased significantly, while the levels of plasma ACTH and CORT, pituitary ACTH, and urine CORT were elevated. Again, APS administration improves these outcomes and returns their levels to normal. Thus, the glucose and lipid metabolic disorder in the high-fat diet and STZ-induced diabetes model may be related to increased HPA axis activity. The hypoglycemic effect of the traditional Chinese medicine, ASP, may improve HPA axis functioning and aid in the treatment of diabetes.

Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine.

BackgroundBerberine is known to improve glucose and lipid metabolism disorders, but it poorly absorbed into the blood stream from the gut. Therefore, the exact underlying mechanism for berberine is still unknown. In this study, we investigated the effect of berberine on glucose metabolism in diabetic rats and tested the hypothesis that berberine acts directly in the terminal ileums.MethodsRats were divided into a control group, diabetic group (DM), low dose of berberine group (BerL) and high dose of berberine group (BerH). Ileum samples were analyzed using a Roche NimbleGen mRNA array, qPCR and immunohistochemistry.ResultsWe found that 8 weeks of treatment with berberine significantly decreased fasting blood glucose levels. An oral glucose tolerance test (OGTT) showed that blood glucose was significantly reduced in the BerL and BerH groups before and at 30 min, 60 min and 120 min after oral glucose administration. Plasma postprandial glucagon-like peptide-1 (GLP-1) levels were increased in the berberine-treated groups. The ileum from the BerH group had 2112 genes with significantly changed expression (780 increased, 1332 decreased). KEGG pathway analyses indicated that all differentially expressed genes included 9 KEGG pathways. The top two pathways were the MAPK signaling pathway and the GnRH signaling pathway. Q-RT-PCR and immunohistochemistry verified that glucagon-like peptide 1 receptor (Glp1r) and mitogen activated protein kinase 10 (Mapk10) were significantly up-regulated, in contrast, gonadotropin releasing hormone receptor (Gnrhr) and gonadotropin-releasing hormone 1 (Gnrh1) were down-regulated in the BerH group.ConclusionOur data suggest that berberine can improve blood glucose levels in diabetic rats. The mechanisms involved may be in the MAPK and GnRh-Glp-1 pathways in the ileum.

Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats

Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of Tianmai Xiaoke (TMXK) Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action. Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin (50 mg/kg, tail vein). One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction (qPCR). Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance (HOMA-IR) index were also measured. The authors found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. The authors also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression (1 752 increased, 471 decreased). Based on Kyoto encyclopedia of genes and genomes pathway analysis, the most three significant pathways were "insulin signaling pathway", "glycolysis/gluconeogenesis" and "citrate cycle (TCA)". qPCR showed that relative levels of forkhead box O3 (FoxO3), phosphoenolpyruvate carboxykinase 2 (Pck2), and protein tyrosine phosphatase 1B (Ptp1b) were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 (Akt1) and insulin receptor substrate 2 (Irs2) were increased. Our data show that TMXK Tablet reduces fasting glucose level and improves insulin resistance in diabetic rats. The mechanism may be linked to the inactivation of PTP1B and PCK enzymes, or through intracellular pathways, such as the insulin signaling pathway.

Resistant starch promotes vitamin D balance and maintenance of methyl group metabolism in type 1 diabetic rats (1041.8)

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by pancreatic beta cell dysfunction, insulin deficiency and abnormal carbohydrate metabolism. Chronic hyperglycemia causes structural damage to the kidneys, resulting in ultrafiltration and imbalance of nutrients such as vitamin D and disruption of various proteins associated with methyl group metabolism and homocysteine regulation. Using streptozotocin (STZ)‐treated rats as a model of T1DM, we have demonstrated that dietary resistant starch (RS) attenuates many complications associated with T1DM including increased urinary excretion of 25,OH vitamin D and vitamin D binding protein. The focus of this study was to further characterize the impact of RS on vitamin D balance and methyl group metabolism in diabetic rats. Female rats (n=36) were randomly assigned to 1 of 3 groups: control, T1DM and T1DM + dietary RS. Control and T1DM rats were fed a standard cornstarch diet during the 8‐wk treatment period, whereas T1DM + RS groups were fed a high amylose cornstarch diet (36% resistant to digestion). T1DM rats exhibited polyuria, hyperglycemia, decreased urinary creatinine excretion (2.3 fold) and increased hepatic (1.2 fold) and renal (~2 fold) GNMT activity. Dietary RS attenuated these complications. Future research will focus on understanding the mechanism by which dietary RS promotes regulation of vitamin d and methyl group metabolism.Body characters no spaces: 1217 / Body characters with spaces: 1428 Total characters no spaces: 1455Grant Funding Source: Supported by Plant Sciences Institute, Iowa State University

Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability

Low oral bioavailability of berberine due to poor solubility and membrane permeability limits its clinical use for treatment of diabetes. We developed an amorphous solid dispersion of berberine with absorption enhancer sodium caprate, referred to as Huang-Gui Solid Dispersion (HGSD) preparations, and examined them for improvement of dissolution and oral bioavailability. HGSDs were prepared by solvent evaporation, and the formulations of amorphous solid dispersions were characterized by X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. According to in vitro solubility and dissolution studies, P9, the 9th production of HGSDs based on orthogonal test, was sorted out. Then pharmacokinetic behavior of P9 was evaluated by in vitro membrane permeation, in situ intestinal perfusion, and in vivo bioavailability in rats. Furthermore, the anti-diabetic effect of P9 was examined in a type 2 diabetic rat model. It was found that majority of berberine in P9 existed in an amorphous form, and its solubility and dissolution rate were significantly increased. Pharmacokinetic studies demonstrated a 3-fold increase in in vitro membrane permeation, a 4-fold increase in in situ intestinal perfusion and a 5-fold increase in vivo bioavailability of P9 compared to berberine or berberine tablets. In addition, oral administration of P9 (100mg/kg) improved glucose and lipid metabolism in diabetic rats compared to pure berberine (100mg/kg), berberine tablets (100mg/kg) or metformin (300 mg/kg) treatment. These findings indicate that P9 enhances oral bioavailability of berberine and may be a potential candidate drug for treatment of diabetes.

Remodeling intestinal flora with sleeve gastrectomy in diabetic rats.

Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism.