Type-2 Diabetic Rats Research Articles

Effect of Lupeol on the Expression of Neuro Inflammatory Signalling Molecules in Brain Tissues of High Fat Diet and Sucrose Fed Type-2 Diabetic Rats

Lupeol has anti- inflammatory, antimicrobial, anti-protozoal, anti-proliferative, anti-invasion, anti-angiogenic and cholesterol-lowering properties. However, the mechanisms underlying the effect of lupeol on neuroinflammatory signalling molecules have not yet been identified. The study was designed to study the effect of lupeol on the expression of inflammatory signalling molecules in brain tissue of high-fat diet and sucrose-fed type-2 diabetic rats. Adult male albino rats of Wistar 150–180 days old with 180–200 g body weight (b.wt) were divided into four groups of six rats each. Group I: Control (vehicle-treated): Group II: High fat diet-induced type-2 diabetic rats; Group III: Type-2 diabetic rats treated with lupeol (25 mg/kg b.wt/day) orally for 30 days and Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg, b.wt/day orally for 30 days. After 30 days of treatment, the animals were anaesthetized, and brain tissue was dissected and used for the assessment of mRNA expression analysis. Type-2 diabetic animals showed a significant increase (p<0.05) in TNF-α and IL-6 mRNA levels in brain tissue in high-fat diet-induced type-2 diabetic animals. However, lupeol treatment, effectively reduced (p<0.05) the neuroinflammatory signaling molecules (TNF- α and IL-6 mRNA) showing that lupeol has significant role over the control of neuroinflammatory signaling. Our present findings clearly show that lupeol has a significant role in reducing neuroinflammation via the downregulation of TNF-α and IL-6 in brain tissues and hence, lupeol can be a potential natural drug for the treatment of diabetic neuropathy.

Argyreia nervosa Mitigates Insulin Resistance in Liver via IR/IRS-1 Mediated Signaling in Streptozotocin-Induced Type-2 Diabetic Rats

Argyreia nervosa, commonly known as Hawaiian baby woodrose or wooly morning glory, is a plant native to India and is also found in various parts of the world. It is known for its seeds, which have been used traditionally in Ayurvedic and traditional medicine systems for various diseases. The study was aimed at assessing the effect of Argyreia nervosa on insulin signaling molecules of the liver in streptozotocin (STZ)-induced experimental type-2 diabetic rats. Healthy adult male Wistar albino rats -150-180 days old weighing 180-200g was used for the study and divided as Group I - Normal rats; Group II – type-2 diabetic rats; Group III -Diabetic rats + A. nervosa 500 mg/kg b.wt; Group IV-Normal rats + A. nervosa 500 mg/kg b.wt. Fasting blood glucose, and fasting serum insulin were measured by calorimetric methods. Further mRNA expression analysis of insulin receptor (IR) was measured in control and treated animals by quantitative Ream Time PCR analysis. A. nervosa root extract significantly reduced fasting blood glucose and serum insulin concentrations in STZ-induced rats compared with control. In addition, mRNA expression of IR showed a one-fold increase in the expression which shows that A. nervosa is involved in the regulation of insulin signaling in the liver and thereby reduces insulin resistance and type-2 diabetes. Our study concludes that A. nervosa root extract has a significant role on insulin signaling molecules thereby it reduces hyperglycemia and hyperinsulinemia via insulin receptor-mediated pathways. Hence, A. nervosa may be considered as one of the therapeutic natural antidiabetic drugs.

Low-fat cheese ameliorates glucose intolerance and normalizes insulin secretion in a rat model of type 2 diabetes by promoting β-cell recovery.

We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet (HFD) and streptozotocin (STZ) to elicit T2D were hyperglycemic. One week after STZ injection, low-fat (LOW) or regular-fat (REG) cheese was provided for 5 weeks and compared with T2D and low-fat diet reference (REF) groups. Food intake and weight gain were similar in all groups. Oral glucose tolerance tests revealed glucose intolerance in T2D rats that was partially ameliorated by LOW but not REG. Insulin secretion during the oral glucose tolerance test was impaired in T2D and REG at 10min (p<0.05) but the iAUC was highly variable in all groups and statistical differences were not detected (p>0.05). β-cell mass and pancreatic insulin content in T2D and REG were 50% lower than REF (p<0.05), whereas LOW was not significantly different. Although isolated islets from all groups responded to glucose, the absolute amount of insulin secreted by T2D and REG was markedly reduced compared with REF, while LOW islets had relatively normal secretion. In conclusion, LOW but not REG cheese enhanced β-cell recovery from HFD/STZ treatment that led to amelioration of glucose tolerance within 5 weeks.

Effect of ß- Caryophyllene on Urocortin-3 expression in adipose tissue of high fat diet and fructose-induced type-2 diabetic rats.

Effect of ß- Caryophyllene on Urocortin-3 expression in adipose tissue of high fat diet and fructose-induced type-2 diabetic rats.

Aerobic training with moderate or high doses of vitamin D improve liver enzymes, LXRα and PGC-1α levels in rats with T2DM

Dysregulation of key transcription factors involved in hepatic energy metabolism, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and liver X receptor alpha (LXRα), has been observed in T2DM. The present study aims to investigate the effects of aerobic training and vitamin D supplementation on liver enzyme levels and the levels of PGC-1α and LXRα proteins in hepatocytes, in a rat model of T2DM. The study involved 56 male Wistar rats, divided into two groups: one was non-diabetic and acted as a control group (n = 8), and the other had induced diabetes (n = 48). The diabetic rats were then split into six subgroups: two groups received high or moderate doses of vitamin D and aerobic training (D + AT + HD and D + AT + MD); two groups received high or moderate doses of vitamin D alone (D + HD and D + MD); one group underwent aerobic training with vehicle (sesame oil; D + AT + oil), and one group was a diabetic control receiving only sesame oil (oil-receiving). The D + AT + HD and D + HD groups received 10,000 IU of vitamin D, while the D + AT + MD and D + MD groups received 5000 IU of vitamin D once a week by injection. The D + AT + oil group and the sham group received sesame oil. After eight weeks of treatment, body weight, BMI, food intake, serum insulin, glucose, 25-hydroxyvitamin D, ALT, AST, and visceral fat were measured. The levels of PGC-1α and LXRα proteins in the liver was assessed by western blotting. Statistical analysis was performed using the paired t-test, one-way analysis of variance (ANOVA), and the Tukey post hoc test at a significance level of P < 0.05. Body weight, food intake, and BMI decreased significantly in the D + AT + HD, D + AT + MD, D + AT + oil, D + HD, and D + MD groups with the highest reduction being observed in body weight and BMI in the D + AT + HD group. The D + AT + HD group exhibited the lowest levels of insulin, glucose, and HOMA-IR while the D + C group exhibited the highest levels among the diabetic groups. The D + AT + HD and D + AT + MD groups had lower levels of ALT and AST enzymes compared to the other groups with no significant difference between D + AT + HD and D + AT + MD. D + AT + HD (p = 0.001), D + AT + MD (p = 0.001), D + HD (p = 0.023), D + MD (p = 0.029), and D + AT + oil (p = 0.011) upregulated LXRα compared to D + C. Among these groups, D + AT + HD exhibited a more profound upregulation of LXRα than D + AT + MD, D + AT + oil, D + HD, and D + MD (p = 0.005; p = 0.002, p = 0.001, and p = 0.001, respectively). Similarly, D + AT + HD showed a more notable upregulation of PGC-1α compared to D + AT + oil, D + HD, and D + MD (p = 0.002; p = 0.001, and p = 0.001, respectively). Pearson correlation tests showed significant and negative correlations between serum 25-hydroxyvitamin levels and both visceral fat (r = − 0.365; p = 0.005) and HOMA-IR (r = − 0.118; p = 0.009); while positive and significant correlations between the liver-to-bodyweight ratio with both ALT and AST enzymes and also between QUICKI levels with LXRα (r = 0.578; p = 0.001) and PGC-1α (r = 0.628; p = 0.001). Combined administration of aerobic training and vitamin D supplementation potentially improves liver enzymes in type-2 diabetic rats that were simultaneous with upregulating the levels of PGC-1α and LXRα proteins in hepatocytes. These improvements were more significant when combining exercise with high-dose vitamin D supplementation. This study highlights the potential of this combination therapy as a new diabetes treatment strategy.

Evaluating the effectiveness of a novel somatostatin receptor 2 antagonist, ZT-01, for hypoglycemia prevention in a rodent model of type 2 diabetes.

Background: Elevated levels of somatostatin blunt glucagon counterregulation during hypoglycemia in type 1 diabetes (T1D) and this can be improved using somatostatin receptor 2 (SSTR2) antagonists. Hypoglycemia also occurs in late-stage type 2 diabetes (T2D), particularly when insulin therapy is initiated, but the utility of SSTR2 antagonists in ameliorating hypoglycemia in this disease state is unknown. We examined the efficacy of a single-dose of SSTR2 antagonists in a rodent model of T2D. Methods: High-fat fed (HFF), low dose streptozotocin (STZ, 35mg/kg)-induced T2D and HFF only, nondiabetic (controls-no STZ) rats were treated with the SSTR2 antagonists ZT-01/PRL-2903 or vehicle (n = 9-11/group) 60min before an insulin tolerance test (ITT; 2-12U/kg insulin aspart) or an oral glucose tolerance test (OGTT; 2g/kg glucose via oral gavage) on separate days. Results: This rodent model of T2D is characterized by higher baseline glucose and HbA1c levels relative to HFF controls. T2D rats also had lower c-peptide levels at baseline and a blunted glucagon counterregulatory response to hypoglycemia when subjected to the ITT. SSTR2 antagonists increased the glucagon response and reduced incidence of hypoglycemia, which was more pronounced with ZT-01 than PRL-2903. ZT-01 treatment in the T2D rats increased glucagon levels above the control response within 60min of dosing, and values remained elevated during the ITT (glucagon Cmax: 156 ± 50 vs. 77 ± 46pg/mL, p < 0.01). Hypoglycemia incidence was attenuated with ZT-01 vs. controls (63% vs. 100%) and average time to hypoglycemia onset was also delayed (103.1 ± 24.6 vs. 66.1 ± 23.6min, p < 0.05). ZT-01 administration at the OGTT onset increased the glucagon response without exacerbating hyperglycemia (2877 ± 806 vs. 2982 ± 781), potentially due to the corresponding increase in c-peptide levels (6251 ± 5463 vs. 14008 ± 5495, p = 0.013). Conclusion: Treatment with SSTR2 antagonists increases glucagon responses in a rat model of T2D and results in less hypoglycemia exposure. Future studies are required to determine the best dosing periods for chronic SSTR2 antagonism treatment in T2D.

Antidiabetic and Thrombolytic Activities of Some Selected Medicinal Plants in High Fat Diet and Dexamethasone-Induced Type 2 Diabetic Rats

Background: Type-2 diabetes (T2D) is a hypercoagulable and hypofibrinolytic condition that predisposes to cardiovascular and thrombotic complications. We screened three medicinal plants (Albizzia chevalieri, Newbouldia laevis and Leptadenia hastate) for their antidiabetic and thrombolytic activities.&#x0D; Methods: T2D was induced with high fat diet and dexamethasone. Following induction, rats were grouped into 6 (n=8 rats); control, untreated, treated (500mg/kg body weight (BW) metformin only) or treated (300mg/kg BW leaf extracts). The rats were treated for two weeks and euthanized. About 2ml of the collected blood was used for thrombolytic activity assay while the rest was processed, and the recovered serum utilised for biochemical and hormonal assays.&#x0D; Results: Rats treated with extracts had significantly (p&lt;0.05) lowered concentrations of serum glucose, TG, LDL-cholesterol, VLDL- cholesterol and increased HDL-cholesterol compared to untreated rats. Extracts also lowered (p&lt;0.05) the serum insulin concentration on day 14 compared to untreated rats. Albizzia chevalieri, Newbouldia laevis and Leptadenia hastata showed 48.90%, 39.20% and 37.69% clot lysis activities respectively which was significantly higher (p&lt;0.001) than distilled water, while streptokinase produced a substantial clot lysis of 93.70%.&#x0D; Conclusions: The leaf extracts of Albizzia chevalieri, Newbouldia laevis and Leptadenia hastata have antidiabetic and thrombolytic activities in type-2 diabetic rats and thus, can be potentially used as combined antidiabetic and thrombolytic agents with in vivo effects in type-2 diabetic patients.

Hepatoprotective Effect of Extra Virgin Olive Oil and Apple Cider Vinegar in Type-2 Diabetic Rat Model

Introduction: Type-2 diabetes mellitus, a major public health problem, is caused by insulin resistance. In diabetics, chronic hyperglycemia results in formation of reactive oxygen species. Oxidative stress in diabetic patients is responsible for hepatic damage because it causes activation of several pro-inflammatory mediators in liver. Hepatic complications of diabetes include fatty liver disease, necrosis, cirrhosis, carcinoma and liver failure. Aims &amp; Objectives: To determine and compare the hepatoprotective effect of extra virgin olive oil and apple cider vinegar in streptozotocin induced Type-2 diabetic rat model. Place and Duration of Study: This experimental study was conducted at Animal House of Postgraduate Medical Institute, Lahore, Pakistan from May 2021 to June 2021. Material &amp; Methods: In this study, 40 male Sprague Dawley rats were divided into 4 groups i.e., Group I was NC (negative control), Group II PC (positive control), Group III EVOO (Extra virgin olive oil) and Group IV (Apple cider vinegar), each group having 10 rats. Diabetes was induced in all rats except the rats of NC group at the start of the study by intraperitoneal administration of injection nicotinamide, followed by injection STZ after 15 minutes. Group III was given 1ml/100gBW/ day EVOO and Group IV was given 2ml/kgBW/day diluted ACV with distilled water in 1:5 orally for 4 weeks. Terminal sampling was performed at the end of the 4th week for estimation of liver enzymes (ALT, ALP and AST) in serum. Data were entered and analyzed in SPSS version 26. p value of ? 0.05 was considered significant. Results: On comparison with PC group, both the treatment groups showed significant decrease in serum ALT levels with p values 0.026 for EVOO and &lt; 0.001 for ACV. Serum ALP levels were also decreased significantly in both the treated groups with p value &lt; 0.001 for EVOO as well as for the ACV group. However, reduction in serum AST levels was nonsignificant with p values 0.082 and 0.058 in EVOO and ACV groups respectively. Conclusion: Both EVOO and ACV have hepatoprotective effect in Type-2 diabetic rats. However, ACV is more effective.

THE IMPACT OF METABOLISM DYSREGULATION IN SCAFFOLD-GUIDED LARGE-VOLUME BONE REGENERATION

The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume bone regeneration. Our study treated wild-type or T2D rats with 5 mm critical-sized femoral defects with 3D-printed polycaprolactone (PCL) scaffolds with 70% porosity. Metabolomics was leveraged for a holistic view of metabolism alteration as healing progress and correlated to regenerated bone tissue volume and quality assessed using micro-computed tomography (µ-CT), histology, and immunohistology. Semi-targeted metabolomics analysis indicated dysregulation in the glycolysis and TCA cycle – the main energy production pathways, in T2D compared to healthy animals. The abundance of metabolites substrates, i.e., amino acids – for protein/ extracellular matrix synthesis was also affected in T2D. Tissue-level metabolites observations aligned with morphological observation with less newly formed bone observed in T2D than wild-type rats. This study enlightens the metabolism landscape during scaffold-guided large-volume bone regeneration in wild-type vs. T2D to further guide the personalization of the scaffold to drive successful regeneration.

Antidiabetic and antioxidant potential of Crocin in high-fat diet plus streptozotocin-induced type-2 diabetic rats.

Crocin, the principal water-soluble active constituent of saffron, possesses numerous pharmacological activities. The present investigation examined the potential antidiabetic and antioxidant characteristics of Crocin in rats with type-2 diabetes by administering it orally and intraperitoneally (i.p.). After 2weeks of a high-fat diet, streptozotocin (STZ) (i.p., 40mg/kg) was administered to male adult rats to induce type-2 diabetes mellitus. Body weight and fasting blood glucose (FBG) were measured on days zero, weeks 1, and 2. At the end of 2 weeks of drug administration in their respective groups, fasting insulin and glucose levels were estimated, and insulin resistance (HOMA-IR) was determined. Intraperitoneal glucose (IPGTT) and insulin tolerance tests (ITT) were carried out. Histopathological investigation and biochemical parameters were estimated in pancreatic tissues. The Crocin (100mg/kg) treatment has significantly improved body weight, abatement of FBG, fasting insulin, and HOMA-IR. Likewise, Crocin treatment significantly improved the glucose and insulin challenges. We observed a significantly marked elevation in endogenous antioxidant enzymes in Crocin-treated groups. Similarly, Crocin treatment reversed the histopathological changes and restored the normal integrity and function of the pancreas. The overall finding indicates that intraperitoneal administration of Crocin demonstrated better control of glycemic level and body weight. Further, it has improved insulin levels in the serum and potentiated antioxidant properties.

Tea polyphenols improves depression-like behavior in aged type 2diabetes rats by regulating microglia polarization

To investigate the effect of tea polyphenols(TP) on improving depression-like behavior in aged type 2 diabetes(T2DM) model rats. A total of 40 8-week-old SD male rats were randomly divided into the control group(n=10) and the modeling group(n=30) according to the body weight. The rats in the modeling group were fed with high-glucose and high-fat diet and treated with 50 mg/kg D-galactose by intraperitoneal injection daily until the end of the experiment, while the rats in the control group were fed with the standard diet and treated with an equal volume of saline by intraperitoneal injection. After 4 weeks, the rats in the modeling group were injected with 25 mg/kg STZ, meanwhile the rats in the control group were injected with an equal volume of citric acid buffer. The level of fasting blood glucose(FBG) was measured on the 14~(th) day. When FBG≥16.7 mmol/L, the rats were identified as successful model of the T2DM rats. Then, the model rats were randomly divided into the model group, 150, 300 mg/kg TP groups(n=10, respectively), and the rats were given intragastric intervention for 8 weeks. The levels of the FBG were detected, and the depression-like behavior of rats was assessed by the open field test(OFT) and forced swimming test(FST). The density of microglia in hippocampus CA1 region was assessed by immunofluorescence staining, and protein expressions of P53, Iba1, iNOS, Arg-1 and BDNF were determined by western blot. Compared with the control group, the levels of FBG in the rats of the model group were obviously increased(P&lt;0.01). In the OFT, the frequencies of rearing and grooming in the rats of model group markedly was decreased, while in the FST, the immobility time extensively was increased(P&lt;0.01). The density of microglia in hippocampus CA1 region was increased(P&lt;0.01). The expressions of P53, Iba1 and iNOS were increased, and the expressions of Arg-1 and BDNF were decreased(P&lt;0.01). Additionally, compared with the model group, in the OFT, the frequencies of rearing and grooming were increased in the rats in 150 and 300 mg/kg TP group(P&lt;0.01). The density of microglia in hippocampus CA1 region was decreased(P&lt;0.01). The expressions of P53, Iba1 and iNOS were down-regulated, and the expression of BDNF was up-regulated(P&lt;0.01). Additionally, compared with the model group, the levels of FBG was decreased in the rats in the 300 mg/kg TP group(P&lt;0.01). The immobility time was decreased in the FST(P&lt;0.01). The expression of Arg-1 was down-regulated(P&lt;0.01). TP can improve depression-like behavior in aged T2DM model rats, and its mechanism may be related to regulate microglia M1/M2 polarization and up-regulate expression of BDNF in hippocampus.

Molecular Approach to Identify Anti-inflammatory Potential of Stevioside in HFD-induced Type 2 Diabetic Rats: Evidence From in Vivo Study

Stevioside is a natural sweetener derived from the leaves of the Stevia rebaudiana plant. It has gained popularity as a sugar substitute due to its intense sweetness without adding calories or affecting blood sugar levels, making it a suitable option for people with diabetes or those looking to reduce their sugar intake. Studies have shown that stevioside has glucose lowering effects. Previous studies have shown that it has significant role in skeletal muscle but its role on expression of inflammatory signaling molecules in adipose tissue against high diet and sucrose-induced type-2 diabetes in experimental rats is yet to be done. The current research was undertaken to investigate if stevioside could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of stevioside (20 mg/kg b.wt) was administered orally for 45 days to high fat diet and sucrose induced type-2 diabetic rats. Interestingly, stevioside treatment restores the elevated serum levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) in adipocytes of diabetic rats. The gene expression of IR, GLUT4 and PPAR-γ mRNA were also significantly activated in stevioside treated groups but reduced IL-1 beta, IlL-6, IKKB, TNF-alpha and NFkB mRNA expression in diabetic adipose tissue. More importantly, stevioside acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that stevioside inhibits obesity induced insulin resistance by ameliorating the inflammatory events and upregulating insulin signalling molecules. Keywords: Stevioside, HFD-T2DM, pro inflammation, insulin signalling; adipose tissue, obesity; signaling pathways; Therapautics.

Regulation of Intestinal Flora and Immune Response by Cyanidin Exhibits Protective Effect against Type-2 Diabetes in Rat Model.

In the current study the effects of metformin and cyanidin on the immune system and intestinal flora in rats with type-2 diabetes was investigated. The findings showed that metformin or cyanidin treatment considerably reduced the rise in body weight and glucose levels induced by type-2 diabetes. The type-2 diabetic rats' glucose tolerance was significantly increased by cyanidin administration comparable to that of metformin. Cyanidin administration resulted in a significant reduction in serum cholesterol and low-density lipoprotein (LDL) levels in rats with type-2 diabetes. Treatment with cyanidin significantly increased the ratio of high-density lipoprotein to low-density lipoprotein in type-2 diabetes rats. Cyanidin administration significantly raised the ratio of Firmicutes to Bacteroidetes in the fecal samples of type-2 diabetic rats compared to the model group. In comparison to the model group, it also significantly raised the levels of Lactobacillus intestinalis, Lactobacillus gasseri, and Lactobacillus reuteri in the type-2 diabetes rats. In type-2 diabetes rat fecal samples, the abundance of Christensenellaceae significantly increased while Enterobacteriaceae and Proteobacteria were found to decrease upon cyanidin administration. Furthermore, cyanidin administration to the rats with type-2 diabetes significantly improved the glucose homeostasis. In conclusion, the study demonstrates that cyanidin enhances glucose homeostasis in rats with type-2 diabetes, potentially through controlling intestinal flora. Thus, cyanidin may be looked into more as a possible therapeutic agent for type 2 diabetes.

Treatment with Leiurus quinquestratus scorpion venom ameliorates the histopathological changes of type-2 diabetic rats' splenic tissues.

Treatment with Leiurus quinquestratus scorpion venom ameliorates the histopathological changes of type-2 diabetic rats' splenic tissues.

Combinational Antidiabetic effects of Curcuma longa L. and Trigonella foenum-graecum L. extracts in alloxan induced type-1 diabetic rats

Diabetes mellitus is a metabolic disorder that is one of the leading causes of death globally. The current study aimed to determine the combined protective effect of Curcuma longa (CL) and Trigonella foenum-graecum (TFG) on alloxan-induced oxidative stress in liver tissue of albino Wister rats. Rats were divided into 8 groups with 6 individuals each. Group I served as control, group II, III and IV were treated with CL, TFG and CL+TFG respectively. Group V, VI, VII and VIII were alloxan-induced diabetic rats, whereas group V served as negative control and group VI, VII and VIII were treated with CL, TFG and CL+TFG respectively. Blood glucose, body weight, oxidative enzymes and histopathological changes were evaluated. Group V showed significant increase in blood glucose levels after induction of alloxan, whereas, group VI, VII and VIII showed significantly decreased levels. However, the best hypoglycaemic activity was found in group VIII. The body weights were slightly increased in groups II, III and IV after the treatment of plant extracts, whereas, decreased body weights were noticed in group V. though no significant weight changes were observed in groups VI, VII and VIII. A significant decrease in oxidative enzyme levels as compared to group V were recorded. The histopathological investigation of liver tissue showed morphological alteration in group V and ameliorative effects in group VI, VII and VIII due to administration of CL, TFG and CL+TFG. Therefore, the combined administration of CL+ TFG exhibits the highest hypoglycemic activity by reducing the oxidative enzyme levels and regeneration of liver tissue.

Colonic L-cell impairment in aged subjects with type 2 diabetes leads to diminished GLP-1 production

AimsGlucagon-like peptide 1 (GLP-1) is produced by the L subtype of enteroendocrine cells (EECs). Patients with type 2 diabetes (T2D) exhibit reduced incretin effect, but the pathophysiology and functional change of the L-cells remain unclear. Deciphering the mechanisms of the biological changes in L-cells under T2D conditions may assist in the research of gut-based strategies for T2D therapy. MethodsWe investigated the fasting serum GLP-1 levels and the distribution of colonic L-cells in young and aged participants with and without T2D. Additionally, we established an aged male T2D Wistar rat model subjected to a long-term high-fat and high-fructose (HFHF) diet. Histological investigations and single-cell RNA sequencing (scRNA-seq) analyses were performed to explore the mechanisms underlying functional changes in the colonic EECs. ResultsWe observed a decline in circulating GLP-1 levels and a reduced number of colonic L-cells in elderly patients with T2D. The mechanisms underlying impaired L-cell formation and disturbed GLP-1 production were revealed using aged T2D rats induced by a long-term HFHF diet. The scRNA-seq results showed that the transcription factors that regulate L-cell commitment, such as Foxa1, were downregulated, and the expression of genes that participate in encoding GLP-1, GLP-1 posttranslational processing, hormone secretion, and nutrient sensing was disturbed. ConclusionsTaken together, the reduced L-cell lineage commitment and disturbed L-cell functions might be the major cause of the reduced GLP-1 production in aged populations with T2D. Our study provides new insights for identifying novel targets in colonic L-cells for improving endogenous GLP-1 production.

ß- Caryophyllene Ameliorates Insulin Resistance in Liver of High Fat Diet and Fructose-Induced Type-2 Diabetic Rats

Insulin resistance may impact organs that transmit insulin signals, like skeletal muscle, adipose tissue, and the liver. Hyperglycemia and hypertriglyceridemia in the fasting state of type 2 diabetes mellitus are more significantly impacted by insulin resistance in the liver. Hypertriglyceridemia is the culprit behind beta-cell failure in type 2 diabetes. Treating insulin resistance in liver as a primary mechanism of traditional antidiabetic drugs, but unfortunately traditional drugs has unalterable advisory effect. In the present research, insulin resistance in the liver is addressed with the versatile natural phytonutrient beta-caryophyllene to demonstrate effectiveness in managing diabetes. An effective dose of -Caryophyllene taken by non-parental route (200 mg/kg b.wt) was given for 30 days to experimentally induced (high-fat diet and fructose-fed) type-2 diabetic rats to find out whether β-Caryophyllene regulates the IRS-2/akt pathway of insulin signaling. In the liver of diabetic rats, the data demonstrates that ß-caryophyllene treatment significantly increased the mRNA and protein expression of insulin receptor (IR) and GLUT-2. However, there was a significant variation in the mRNA expression of akt and insulin receptor-substrate-2 (IRS-2) between groups. Taking caryophyllene supplements can be beneficial for the control of type 2 diabetes. Studies conducted with this sesquiterpene could have tremendous potential and benefit for the treatment of type 2 diabetes.

Identification of Andrographolide as an Agonist of Bile Acid TGR5 Receptor in a Cell Line to Demonstrate the Reduction in Hyperglycemia in Type-1 Diabetic Rats.

Andrographolide (ADG) is contained in bitter plants, and its effects are widely thought to be associated with taste receptors. The current study used animal studies and cell lines to investigate the role of ADG in diabetic models. The Takeda G-protein-coupled receptor (TGR5) was directly influenced by ADG, and this boosted GLP-1 synthesis in CHO-K1 cells transfected with the TGR5 gene. However, this was not seen in TGR5-mutant cells. The human intestinal L-cell line NCI-H716 showed an increase in GLP-1 production in response to ADG. In NCI-H716 cells, the TGR5 inhibitor triamterene reduced the effects of ADG, including the rise in TGR5 mRNA levels that ADG caused. Additionally, as with the antihyperglycemic impact in type-1 diabetic rats, the increase in plasma-active GLP-1 level caused by ADG was enhanced by a DPP-4 inhibitor. The recovery of the hypoglycemic effect in diabetic rats and the increase in plasma GLP-1 caused by ADG were both suppressed by TGR5 blockers. As a result, after activating TGR5, ADG may boost GLP-1 synthesis in diabetic rats, enhancing glucose homeostasis. In Min-6 cells, a pancreatic cell line grown in culture, ADG-induced insulin secretion was also examined. Blocking GLP-1 receptors had little impact, suggesting that ADG directly affects TGR5 activity in Min-6 cells. A TGR5 mRNA level experiment in Min-6 cells further confirmed that TGR5 is activated by ADG. The current study revealed a novel finding suggesting that ADG may activate TGR5 in diabetic rats in a way that results in enhanced insulin and GLP-1 production, which may be helpful for future research and therapies.

Ngu-Vi-Tieu-Khat decoction, a Vietnamese traditional medicine, possesses hypoglycemic and hypolipidemic effects on streptozotocin-induced type-2 diabetic rat model

This study aims to assess the hypoglycemic effects of Ngu-Vi-Tieu-Khat (NVTK) decoction, a traditional Vietnamese medicine, in a rat model of type-2 diabetes. The NVTK decoction was prepared using the maceration method and tested for its hypoglycemic effects by measuring blood glucose levels, insulin resistance indicators, and pancreatic mass. The results showed that NVTK decoction improved diabetes symptoms, increased insulin levels, reduced insulin resistance, restored pancreatic mass, and decreased total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C). The hypoglycemic effects of NVTK were comparable to those of gliclazide at a dose of 10 mg/kg. In conclusion, NVTK decoction possesses hypoglycemic properties and could be explored as a potential traditional medicine for treating type-2 diabetes in humans.

Actinidia deliciosa Extract as a Promising Supplemental Agent for Hepatic and Renal Complication-Associated Type 2 Diabetes (In Vivo and In Silico-Based Studies).

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However, the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway. Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic acid, and melezitose as components of kiwi extract that docked well with potential as effective natural products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the treatment of diabetic hepatorenal complications.