Metabolism In Diabetic Rats Research Articles

Moderate-intensity continuous training and high-intensity interval training alleviate glycolipid metabolism through modulation of gut microbiota and their metabolite SCFAs in diabetic rats

Glucose and lipid metabolism disorders are typical of diabetic patients and are important factors leading to macrovascular and microvascular complications. The aim of this study was to understand the effects of different exercises on glycolipid metabolism in diabetic rats and the role of gut flora in metabolic maintenance. We measured glycolipid metabolic indices and short-chain fatty acids (SCFAs) content and sequenced and analyzed gut microbes after 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) programs in type 2 diabetic rats(T2DM). We found that Enterococcaceae, Enterococcus, Subdoligranulum, Kurthia, Bacillales, and Planococcaceae may be key bacterial taxa related to T2DM and that both programs of exercise regulated the intestinal flora of rats with T2DM, improved their glycolipid metabolism, increased the abundance of SCFA-producing intestinal bacteria, and it was found that the PWY-5676 and P163-PWY pathways which are closely related to production of SCFAs were significantly upregulated in the exercise groups. Notably, MICT appeared to be more effective than HIIT in increasing the homogeneity of rat intestinal flora, enriching species, and increasing acetic acid and butyric acid content. These results suggest that exercise improves glycolipid metabolism in diabetic rats, which may be attributed to alterations in the structure of their intestinal flora.

Regulation of carbohydrate metabolism and insulin secretion in diabetic rats following treatment with Hypericum perforatum L. hairy root aqueous methanol extract

Hairy root (HR) cultures of Hypericum perforatum L. have shown promise in controlling hyperglycemia, regulating blood lipid and enzyme profiles, and improving metabolic function in vivo. These benefits are mainly attributed to the phenolic acids, flavonoids, and xanthones present in HR extracts. However, the specific mechanism underlying these effects remains unclear. This study was performed to elucidate the biochemical and molecular mechanisms driving HR the antihyperglycemic and antidiabetic effects of HR extracts. HR extract (200 mg/kg body weight) was administered daily for 14 days to healthy rats and rats with streptozotocin-induced diabetes, with glibenclamide serving as a positive control. The phenolic composition of the HR extracts was confirmed through high-performance liquid chromatography/diode array detection/electrospray ionization mass spectrometry (HPLC/DAD/ESI-MSn ) analysis. The results showed that HR extract treatment increased the plasma insulin level and pancreatic poly (adenosine diphosphate-ribose) polymerase (PARP) activity in diabetic rats, thus normalizing blood glucose levels. Additionally, it reduced the activity of gluconeogenic enzymes, increased the activity of glycolytic enzymes, and normalized the glycogen content in the liver. HR extract-treated rats also exhibited increased hepatic adenosine monophosphate-activated protein kinase (AMPK) mRNA expression and a decreased protein kinase Cε (PKCε) concentration. In conclusion, HR extract demonstrated insulinotropic effects and effectively regulated hepatic carbohydrate metabolism in diabetic rats by modulating AMPK expression and the PKCε concentration. These findings suggest the potential use of HR extract as an herbal medicine for diabetes treatment and a source of antidiabetic drug development.

Effect of Ginger on Cardiac Oxidative Stress and Carbohydrate Metabolic Profiles in STZ Induced Diabetic Rats

The purpose of this research was to investigate how ginger can protect oxidative stress (antioxidant status) and carbohydrate metabolism in rats with induced diabetes. In this study we observed in diabetic rats, activities of SOD, CAT, GSH content, total carbohydrates, and total proteins decreased, while glycogen content was increased. However, administering ginger to diabetic rats led to an improvement in antioxidant status, total carbohydrates, total proteins and a decrease in glycogen levels. These results indicate that ginger has antioxidant and other medicinal properties that can regulate carbohydrate metabolism in diabetic rats.

Ileum excision partially reverses improvement of glucose metabolism in diabetic rats after biliopancreatic diversion with duodenal switch

BackgroundBile acids can stimulate the secretion of glucagon-like peptide-1 (GLP-1) and be mostly reabsorbed in the ileum. ObjectivesWe aimed to investigate whether ileum excision could reverse the glucose improvement after biliopancreatic diversion with duodenal switch (BPD/DS). SettingPeking Union Medical College Hospital. MethodsThirty diabetic rats were randomly divided into the BPD/DS group, BPD/DS plus ileectomy (BDI) group, and control group. The fasting blood glucose, bile acids, and glucagon-like peptide-1(GLP-1) levels in plasma samples were analyzed. ResultsIn postoperative week 20, the fasting blood glucose level in the BDI group was significantly higher than that in the BPD/DS group (11.5 ± 1.4 mmol/L versus 7.6 ± 1.0 mmol/L, P < .001), and the AUCOGTT value was also significantly higher than that in the BPD/DS group (2186.1 ± 237.2 mmol/L·min versus 1551.2 ± 136.9 mmol/L·min, P < .001). The plasma level of bile acids in the BDI group was lower than that in the BPD/DS group (P = .012) and was not significantly different from that in the control group (P = .629). The plasma level of GLP-1 in the BDI group was lower than that in the BPD/DS group (P = .009) and was not significantly different from that in the control group (P = .530). Moreover, the intestinal TGR5 expression in the BDI group was significantly lower than that in the BPD/DS group (P < .001). ConclusionsThe results show that excision of the ileum can partially reverse the improvement in glucose metabolism after BPD/DS.

Mango (Mangifera indica L.) seed kernel extract suppresses hyperglycemia by modulating pancreatic β cell apoptosis and dysfunction and hepatic glucose metabolism in diabetic rats.

This study investigated the anti-hyperglycemic action of mango seed kernel extract (MKE) and various mechanisms involved in its actions to improve pancreatic β cells and hepatic carbohydrate metabolism in diabetic rats. An intraperitoneal injection of 60mg/kg of streptozotocin (STZ) followed by 30 consecutive days of treatment with MKE (250, 500, and 1000mg/kg body weight) was used to establish a study group of diabetic rats. Using liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) for identification, 26 chemical compounds were found in MKE and the high-performance liquid chromatography (HPLC) analysis of the MKE also revealed the existence of mangiferin, gallic acid, and quercetin. The results confirmed that in each diabetes-affected rat, MKE mitigated the heightened levels of fasting blood glucose, diabetic symptoms, glucose intolerance, total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C). As demonstrated by a remarkable increment in serum and pancreatic insulin, the diabetic pancreatic β cell function was potentiated by treating with MKE. The effect of MKE on diabetic pancreatic apoptosis clearly reduced the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, which was related to diminished levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Bax and an increase in Bcl-xL protein expression. Furthermore, diabetes-induced liver damage was clearly ameliorated along with a notable reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and abnormal liver histology. By enhancing anti-oxidant superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, MKE alleviated diabetes-induced pancreatic and liver oxidative damage, as demonstrated by diminished levels of malondialdehyde. In minimizing the expression levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase-1 proteins in the diabetic liver, MKE also enhanced glycogen content and hexokinase activity. Collectively, these findings indicate that by suppressing oxidative and inflammatory processes, MKE exerts a potent anti-hyperglycemic activity in diabetic rats which serve to protect pancreatic β cell apoptosis, enhance their function, and improve hepatic glucose metabolism.

Enhanced glucose homeostasis via Clostridium symbiosum-mediated glucagon-like peptide 1 inhibition of hepatic gluconeogenesis in mid-intestinal bypass surgery.

The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood. To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism. Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor. The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota. The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.

Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression.

To explore the underlying mechanism of the anti-diabetic effect of resveratrol (RSV) on regulating glycolipid metabolism in diabetic rats induced by streptozotocin (STZ) and a high-fat diet (HFD). Male Wistar rats were randomized into three groups. Two groups were fed a high-fat diet and intraperitoneally injected with STZ (35 mg/kg), with one group also treated with RSV (30 mg/kg/d), and the third, control group was fed a normal diet. After 12 weeks, blood lipid levels and fasting blood glucose (FBG) were assessed. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The protein expression of hypoxia-inducible factor 1α (HIF-1α) was assessed by Western blotting and immunofluorescence, and the proteins level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), phosphorylated-PDK1 (p-PDK1), phosphorylated-protein kinase B (p-AKT), glucose transporter 1 (GLUT1) and low-density lipoprotein receptor (LDLR) in the liver were analyzed by Western blotting. The mRNA levels of Hif-1α, Glut1 and Ldlr in the liver were determined by RT-qPCR. RSV treatment significantly reduced liver/body weight ratio (L/W, P < 0.05), FBG (P < 0.01) and serum concentrations of total cholesterol (TC, P < 0.05), triglycerides (TG, P < 0.01) and low-density lipoprotein-cholesterol (LDL-C, P < 0.05) in diabetic rats. RSV also improved diabetic symptoms, attenuated liver steatosis and increased liver glycogen accumulation. RSV treatment significantly downregulated the proteins expression of p-PDK1 and p-AKT (P < 0.01) and the levels of HIF-1α (P < 0.05) and GLUT1 (P < 0.01), while significantly upregulating the level of LDLR (P < 0.05). RSV was effective in improving glycolipid metabolism in diabetic rats, probably by inhibiting the PDK1/AKT/HIF-1α pathway and regulation of its downstream target levels. These findings may provide new insight into the mechanism of action of RSV in the treatment of diabetes.

Urtica dioica (Gazaneh) distillate restores glucose metabolism in diabetic rats.

Diabetes has become an important health problem in the world. Natural agents, with antidiabetic property, are potential candidates for improving diabetes. Urtica Dioica Distillate (UDD) or Araghe Gazaneh is widely used for the treatment of diabetes as per traditional medicine. Despite the tremendous use of UDD as an antidiabetic compound in folk medicine, the antidiabetic effects of UDD has been neglected by medical scientists. In this study, we aimed to evaluate the effects of UDD on the glucose metabolism in diabetic rats. A total of 24 male rats were divided equally into four groups, two treatment and two control groups, each containing normal or Streptozotocin (STZ)-induced diabetic rats. During 4 weeks, control and treatment rats received water or UDD, respectively. Fasting blood sugar (FBS), HbA1c, serum creatinine, blood urea nitrogen, and specific activities of hepatic enzymes including glucokinase (GK), hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), and muscle glucose transporter type 4 (GLUT4) and liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels were measured. FBS and HbA1c increased in diabetic groups. Treatment with UDD significantly lowered FBS and prevented weight loss. Decreased FBS level was associated with higher activity levels of GK and HK in UDD-treated diabetic rats. G6PD-specific activity decreased in diabetic control rats compared to nondiabetic ones, but UDD treatment improved it to the normal levels. A significant decrease in the expression level of GLUT4 was observed in diabetic control rats compared to nondiabetic ones, but UDD increased it to the normal levels. These findings suggest that UDD might exert therapeutic effects against diabetes by improving glucose metabolism and can be used as an alternative or complementary medicine for the treatment of diabetic patients.

Importance of curcumin effect and asprosin level on glucose metabolism in diabetic rats

Asprosin is a new hormone secreted mainly from white adipose tissue. It may be associated with the pathogenesis of obesity, diabetes and some metabolic diseases. The changes in plasma asprosin levels of experimental diabetic rats and the relation of these changes with liver glucose metabolism and some diabetes parameters were investigated, and the effects of metformin, gliclazide or curcumin treatment on plasma asprosin levels were tried. The study was designed as an animal model in diabetic rats The albino rats were divided into five groups. To induce diabetes, a single dose of STZ was injected intraperitoneally. Diabetics rats were treated intragastrically with metformin (D+Metformin group), gliclazide (D+Giliclazide group) or 20 curcumin (D+Curcumin group) for eight weeks. Fasting blood glucose, insulin levels and other parameters were measured. Plasma asporsin levels of untreated diabetic rats increased significantly (P&lt;.001). Although the plasma asprosin levels of diabetic rats treated with the rugs were significantly lower (P&lt;.001). Fasting blood glucose levels of diabetic rats treated with the drugs were found to be remarkably lower than the diabetic control values (P&lt;.001, respectively). There was no significant difference in the insulin levels and HOMA-IR between these three groups. Curcumin treatment provides significant improvements in plasma asprosin level and diabetes parameters. The increase in plasma asprosin level in diabetic rats may be one of the main reasons that facilitate the development of the disease or is responsible for its pathogenesis. Our findings support the idea that curcumin may be an important treatment option for diabetes.

Antidiabetic Properties of Chitosan and Its Derivatives.

Diabetes mellitus is a chronic metabolic disorder. In addition to taking medication, adjusting the composition of the diet is also considered one of the effective methods to control the levels of blood glucose. Chitosan and its derivatives are natural and versatile biomaterials with health benefits. Chitosan has the potential to alleviate diabetic hyperglycemia by reducing hepatic gluconeogenesis and increasing skeletal muscle glucose uptake and utility. Scientists also focus on the glucose-lowering effect of chitosan oligosaccharide (COS). COS supplementation has the potential to alleviate abnormal glucose metabolism in diabetic rats by inhibiting gluconeogenesis and lipid peroxidation in the liver. Both high and low molecular weight chitosan feeding reduced insulin resistance by inhibiting lipid accumulation in the liver and adipose tissue and ameliorating chronic inflammation in diabetic rats. COS can reduce insulin resistance but has less ability to reduce hepatic lipids in diabetic rats. A clinical trial showed that a 3-month administration of chitosan increased insulin sensitivity and decreased body weight and triglycerides in obese patients. Chitosan and COS are considered Generally Recognized as Safe; however, they are still considered to be of safety concerns. This review highlights recent advances of chitosan and its derivatives in the glucose-lowering/antidiabetic effects and the safety.

Sodium houttuyfonate protects against cardiac injury by regulating cardiac energy metabolism in diabetic rats

Diabetic cardiomyopathy is a diabetic complication with complicated pathophysiological changes and pathogenesis and difficult treatment. Sodium houttuyfonate is the adduct of sodium bisulfite and houttuynin, the main volatile component in Houttuynia cordata Thunb, possesses a variety of activities including multiple interventions on inhibiting ventricular remodeling. The study aims to explore effect of sodium houttuyfonate on diabetic myocardial injury and its underlying mechanisms. The diabetes model was established by intraperitoneal injection of streptozotocin at a dose of 85 mg/kg. By intragastric administration for 26 days, sodium houttuyfonate (50 and 100 mg/kg/d) reversed the abnormal serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, improved the abnormal levels of serum aspartate aminotransferase and brain natriuretic peptide, reduced electrocardiogram P-R and QRS interval extension, accelerated the heart rate, decreased serum malondialdehyde content, up-regulated the myocardial energy metabolism including elevated the contents of ATP, ADP, total adenine nucleotides and phosphocreatine in myocardium, decreased AMP/ATP ratio, elevated myocardial Ca2+-Mg2+-ATPase activity, and down-regulated the mRNA expressions of AMP protein activation kinase α2 (AMPK-α2) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). In a conclusion, these results suggest that sodium houttuyfonate can improve cardiac energy metabolism disorder caused by diabetes by increasing cardiac Ca2+-Mg2+-ATPase activity and regulating AMPK signaling pathway, and then attenuates cardiac injury caused by hyperglycemia. In addition, sodium houttuyfonate also has the effects of anti-oxidation and improving abnormal levels of blood lipid.

Impact of High Aspartame and High Fructose Diet on Vascular Reactivity, Glucose Metabolism and Liver Structure in Diabetic Rats

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder, affected by fructose, and artificial sweeteners. Aspartame and fructose are popularly used, by diabetics, as substitutes to glucose. AIM: This study evaluated the effect of high aspartame and fructose on vascular reactivity, glucose, and hepatic metabolism in diabetic rats. MATERIALS AND METHODS: Forty-eight male rats were divided into six groups: Control, control-diabetic, aspartame, aspartame-diabetic, fructose, and fructose-diabetic. After 60 days, blood pressure, vascular reactivity to norepinephrine, Lipid profile, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and Malondialdehyde (MDA) were measured. RESULTS: High aspartame alone or with diabetes, decreased leptin, vascular reactivity, and increased triglyceride, cholesterol, MDA, and fasting blood glucose. Hepatic tissues showed dilated congested vessels, cellular infiltration, decreased Periodic Acid Schiff’s reaction, and increased collagenous fibers. High fructose decreased leptin, high-density lipoprotein, vascular reactivity, and increased cholesterol, Low-density lipoprotein, MDA, glucose, and HOMA-IR. Hepatic tissues showed more fatty infiltration, glycogen deposition, and increased collagenous-fibers. The condition became worse in diabetes-treated rats. CONCLUSION: High aspartame and high fructose diet caused deleterious effects on diabetic rats by atherogenic, oxidative stress, vascular, glucose, and hepatic tissue metabolism impairment.

Explore the Link between the Improvement of Metabolic Indicators in Diabetic Rats with Sleeve Gastrectomy and Changes in the Composition of Intestinal Flora.

Diabetes mellitus (DM) has become a major medical and health problem in my country and even the world. Doctors and patients have gradually realized that a new type of metabolic surgery is a way to treat diabetes. The operation is relatively simple, and the effect of the operation is no less than that of the gastric shunt. The initial hypothesis could not fully explain the blood pressure and blood sugar reduction mechanism in waist and abdominal surgery. According to requirements, they were divided into the sleeve gastrectomy group (SG group, n = 10) and sham operation group (SS group, n = 10), and corresponding measures were taken. Observe their weight changes; perform an oral glucose tolerance test (GB) before surgery and at 2, 8, and 16 weeks after surgery to evaluate the effect of surgery on improving the glucose metabolism. The postoperative GLP-1 specificity curve was detected in the two groups of patients; the immunohistochemical method was used to detect the postoperative changes of the digestive tract l cells in the two groups; RT-PCR was used to detect the mRNA transcription level of the digestive tract GLP-1 receptor. The bodyweight was significantly different 4 weeks after the operation. Food intake and bodyweight were not significantly different between the SG and SS groups. FBG: one week after operation, the SG group was significantly smaller than the SS group. The SS group was significantly lower than the SG group at 12 weeks after operation, and the SS group was significantly lower than the SG group at 14 weeks after operation. The transcription levels of c-kit mRNA and SCF mRNA in jejunum and ileum tissues are significantly different: the transcription levels of c-kit mRNA and SCF mRNA in the SG group are higher than those in the SS group, jejunum and ileum in the SG group. The number of cell 1 was significantly greater than that of the SS group. Sleeve gastrectomy can improve the regulation of the glucose metabolism in diabetic rats. The increase in small bowel motility may be related to the increase in ICC cells, intestinal cells, and GLP after gastric sleeve resection. The increase is in -1R and faster insoluble CHM in bowel motility. It has better contact with cell 1 and GLP-1R and stimulates cell 1 to secrete GLP-1.

Effect of Combined Treatment with Catechin and Quercetin on Hepatic Glucose Metabolism in Diabetic Rats

Effect of Combined Treatment with Catechin and Quercetin on Hepatic Glucose Metabolism in Diabetic Rats

Manno-oligosaccharides from cassia seed gum ameliorate inflammation and improve glucose metabolism in diabetic rats.

Functional oligosaccharides show anti-diabetic effects through inflammation regulation with improved glucose metabolism. In this study, novel prebiotics of manno-oligosaccharides from cassia seed gum (CMOS) were incorporated into the diet of streptozotocin (STZ) plus high-fat and high-sugar diet (HFSD)-induced rats. After feeding for 8 weeks, CMOS (300-1200 mg per kg b.w. per d) significantly ameliorated the fasting blood glucose level (7.1-8.2 mmol L-1) as compared with that of the model group (14.2 mmol L-1), where the area under the oral glucose tolerance test curve was decreased by 20.0%-24.5%. Meanwhile, CMOS prevented STZ plus HFSD-induced damage to islet tissue with a clear and integrated morphology and reduced the glucagon/insulin area ratio (by 97.9% for 300 mg per kg b.w. per d CMOS). CMOS also reduced metabolic endotoxemia and maintained intestinal integrity with recovered mRNA expression of Zo-1 and occludin to the normal comparable level. Upon 16S rDNA sequencing, it was found that CMOS regulated the microbiota composition in the cecum with an increased relative abundance of Bifidobacteria, while that of Shigella was decreased. The molecular mechanisms involved in the anti-diabetic effects of CMOS were further studied. CMOS reduced the mRNA expression of Tlr2 and Tlr4 in the intestines of STZ plus HFSD-induced rats. Meanwhile, Nlrp3 associated inflammasome activation in the intestine and liver with glucose metabolism disorder was inhibited by CMOS, resulting in reduced interleukin-1β secretion (by 38.8-46.4% for CMOS of 300-1200 mg per kg b.w. per d) and inflammation. Furthermore, CMOS regulated the AKT/IRS/AMPK signaling pathway and improved glucose metabolism in the liver. Findings obtained here implicated that CMOS could modulate metabolic-inflammation as a functional dietary supplement.

Anti-obesity and Anti-diabetic Effect of Ursolic Acid against Streptozotocin/High Fat Induced Obese in Diabetic Rats.

Obesity is occurring due to continue taken high fat diet; this is the fast-growing problem reaching epidemic proportion globally. Ursolic acid altered the abnormal glucose metabolism in diabetic rats. In this experimental protocol, we examine ursolic acid (UA) anti-obesity effect against streptozotocin (STZ) and high-fat diet-induced obesity in rats. Orally administered the ursolic acid (2.5, 5 and 10 mg/kg) dose to the hyperglycemic rats for 8 weeks and estimated the blood glucose level at different time intervals. Biochemical, hepatic, lipid, renal and antioxidant parameters were estimated. Traf-4, Mapk-8, Traf-6 and genes such as Ins-1, ngn-3 and Pdx-1 mRNA expression were estimated using qRT-PCR to scrutinize the molecular mechanism in MAPK downstream JNK cascade and insulin pathway signalling pathways. Ursolic acid significantly (p<0.001) down-regulated the blood glucose level at dose dependent manner. Its also reduced the plasma insulin level, non-essential fatty acid and increased the level of adiponectin as compared to obese control group rats. Ursolic acid treated group rats reduced the level of total cholesterol and triglycerides. Ursolic-acid-treated rats have been shown to decrease oxidative stress in pancreatic tissue by restoring the free radical effect of scavenging, suppress the Traf-6, Mapk-8 and Traf-4 mRNA expression, enhance the expression of Pdx-1, Ins-1 and Ngn-3 and ensure the regeneration of pancreas β cells and therefore pancreas insulin. The current result suggested the anti-obese effect of ursolic acid against high fat diet (HFD) induced obese rats via alteration of insulin and JNK signaling pathway.

Influence of Dietary Chitosan Feeding Duration on Glucose and Lipid Metabolism in a Diabetic Rat Model.

This study was designed to investigate the influence of dietary chitosan feeding-duration on glucose and lipid metabolism in diabetic rats induced by streptozotocin and nicotinamide [a non-insulin-dependent diabetes mellitus (NIDDM) model]. Male Sprague-Dawley rats were used as experimental animals and divided into short-term (6 weeks) and long-term (11 weeks) feeding durations, and each duration contained five groups: (1) control, (2) control + 5% chitosan, (3) diabetes, (4) diabetes + 0.8 mg/kg rosiglitazone (a positive control), and (5) diabetes + 5% chitosan. Whether the chitosan feeding was for 6 or 11 weeks, the chitosan supplementation decreased blood glucose and lipids levels and liver lipid accumulation. However, chitosan supplementation decreased plasma tumor necrosis factor (TNF)-α, insulin levels, alanine aminotransferase (ALT) activity, insulin resistance (HOMA-IR), and adipose tissue lipoprotein lipase activity. Meanwhile, it increased plasma high-density lipoproteins (HDL)-cholesterol level, plasma angiopoietin-like-4 protein expression, and plasma triglyceride levels (at 11-week feeding duration only). Taken together, 11-week (long-term) chitosan feeding may help to ameliorate the glucose and lipid metabolism in a NIDDM diabetic rat model.

Effects of oleanolic acid on inflammation and metabolism in diabetic rats

ABSTRACT Diabetes mellitus (DM) is a chronic metabolic disease that threatens the health of the world population. We investigated the effects of oleanolic acid (OA) administration on inflammation status and metabolic profile in streptozotocin (STZ) induced diabetic rats. Four experimental groups were established: healthy rats not administered OA, healthy rats administered OA, diabetic rats not administered OA, diabetic rats administered OA. OA, 5 mg/kg, was administered by oral gavage for 21 days. Serum samples collected at the end of the experiment and analyzed for toll–like receptor–9, interleukin-18, nuclear factor kappa B, malondialdehyde MDA, glucose, total cholesterol, triglycerides, high–density lipoprotein, low-density lipoprotein, calcium, phosphorus, magnesium and potassium. Pancreas tissue was examined for pathology. Induction of DM caused increased serum concentrations of inflammation and oxidative damage markers. DM also caused hyperglycemia-hyperlipidemia and decreased serum concentration of minerals. The islets of Langerhans were degenerated and necrotic. Administration of OA reversed the adverse effects of DM. OA treatment can ameliorate inflammation and oxidative damage due to DM by normalizing hyperglycemia and decreasing TLR-9, IL-18, NF-κB and MDA levels.

Licochalcone E improves insulin sensitivity in palmitic acid-treated HepG2 cells through inhibition of the NLRP3 signaling pathway

Our previous research demonstrated that compound licochalcone E can reduce glucose tolerance and lipid metabolism in diabetic rats, although its mechanism remains unknown. Here, we used palmitic acid (PA) to establish a PA-treated HepG2 model, and then examined glucose uptake, glucose consumption, and blood lipids to evaluate the effects of licochalcone E within the safe dose range in the model. Polymerase chain reaction (PCR) was used to detect the expression levels of key genes associated with liver gluconeogenesis; enzyme-linked immunosorbent assay (ELISA) was deployed to evaluate the concentration of inflammatory factors; and laser confocal microscopy and western blot were used to determine the levels of reactive oxygen species (ROS) and NLRP3 inflammasome signaling pathway-related proteins, respectively. Finally, molecular simulations were exploited to validate the interaction between licochalcone E and the NLRP3 inflammasome. The results demonstrated that licochalcone E showed no toxicity in the dose range of 2.5–40 μM. In this dose range, licochalcone E substantially increased the uptake and consumption of glucose in the insulin resistance model and dose-dependently reduced the concentration of total cholesterol. The PCR results indicated that licochalcone E dose-dependently reduced the expression of Glucose-6-phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (PEPCK) genes and increased the expression of Glucose Transporter 4 (Glut4) in PA-treated HepG2. Moreover, the ELISA results revealed that licochalcone E significantly reduced the expression of TNF-α, IL-1β, and IL-18. Confocal microscopy results showed that licochalcone E dramatically reduced the generation of ROS and the expressions of NLRP3 and its downstream caspase-1 in PA-treated HepG2 model. Western blot results further indicated that licochalcone E significantly reduced the expression of NLRP3, caspase-1 and IL-1β in the model. Additionally, molecular simulations demonstrated that licochalcone E has good binding affinity for the NLPR3 inflammasome. We concluded that licochalcone E has the potential to be used as an insulin sensitizer by reducing the release of ROS and inflammatory factors following inhibition of the NLPR3 signaling pathway.

Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model.

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.