Pancreas Of Diabetic Rats Research Articles

Immunohistochemical and biochemical study of the effect of Rheum ribes on the pancreas of diabetic rats

Background and objective: Reports indicate that Rheum ribes has antihyperglycemic effects. This study aimed to find out the hypoglycemic effects of aqueous extract of Rheum ribes on the pancreatic tissue of diabetic male rats and compare the results of both histological and biochemical findings with that of metformin. Methods: Thirty-two albino male rats were divided into four groups with eight animals for each group; 1st group as normal control, 2nd group as alloxan induced diabetics, 3rd group as diabetic treated with Rheum ribes, and 4th groups as diabetic treated with Metformin. The body weight and fasting blood glucose levels of all the rats were recorded at weekly intervals during the experimental period. Biochemical, histochemical, and immunohistochemical investigations were used. Results: Diabetic rats showed a decrease in serum amylase with marked elevation in blood glucose level. Histological examination of the pancreas from diabetic rats revealed an increase in the thickness of the basement membrane of the blood vessels and capillaries in islets of Langerhans, as well as decreased activity of Beta-cells and increase the activity of Alpha and Delta cells using both Periodic Acid Schiff stain and immunohistochemistry techniques. Administration of aqueous extract of Rheum ribes caused significant and dramatic changes in most of the parameters measured in this study, including an increase in serum amylase, and lowering the level of blood glucose, in comparison to the diabetic group. Conclusion: Daily administration of Rheum ribes significantly reduced blood glucose and caused a marked increase in the activity of Beta-cells, followed by a decrease in the activity of Alpha-cells. The results of tissue structures and serum biochemical estimation indicated that the plant extract has regeneration and repair effects.

Encapsulation of cinnamon oil in whey protein counteracts the disturbances in biochemical parameters, gene expression, and histological picture of the liver and pancreas of diabetic rats.

This study aimed to evaluate the protective role of encapsulated cinnamon oil emulsion (COE) in whey protein concentrate (WPC) against the disturbance in lipid profile, oxidative stress markers, and gene expression in streptozotocin (STZ)-treated rats. COE was analyzed using GC-MS, and the emulsion was prepared and characterized. In the in vivo study, six groups of male rats were treated orally for 4weeks, including the control group, the group treated with STZ (D-rats), the groups received a low or high dose of COE (200 or 400mg/kg B.w.), and the D-rats groups received COE at the low or high dose. Blood and tissue samples were collected after the end of the treatment period for biochemical, genetical, and histological analyses. The GC-MS results revealed that the major components of the oil were cinnamaldehyde, 1,8 cineole, acetic acid, 1,7,7-trimethylbicyclo[2.2.1]hept2yl ester, α-Pinene, and α-Terpineol. The size, zeta potential, and polydispersity index (PDI) of COE were 240 ± 1.03nm, - 7.09 ± 0.42, and 0.36, respectively. The in vivo results revealed that COE at the two tested doses improved the levels of glucose, insulin, amylase, lipid profile, hepatic MDA, SOD, and GSH. COE also downregulated hepatic GLU2, FAS, SREBP-1c, and PEPCK gene expression and upregulated IGF-1 mRNA expression in diabetic rats in a dose-dependent manner. Moreover, COE improved and the histological picture of the liver and pancreas. It could be concluded that COE overcomes the disturbances in biochemical, cytological, and histopathological changes in D-rats via the enhancement of antioxidant capacity; reduces the oxidative stress; modulates the concerned gene expression; and may be promising to develop new drugs for diabetic treatment.

Effect of Propolis Administration on the Endocrine Functions and Histopathology of Pancreas in Streptozotocin-Induced Diabetic Rats

This study was performed to investigate the hypoglycemic properties of Propolis and their possible role on pancreatic's tissue. Diabetes mellitus was induced in 45 adult male albino rats and the animals were divided into three groups; Negative control group received standard diet; Positive group diabetic untreated group; Propolis treated group supplemented with (0.3 g/Kg/day) for 2 weeks after the induction of diabetes by streptozotocin. At the end of the experiment, blood was collected from the abdominal aorta. A heparinized tube was used for collection of plasma for measurement of lipid peroxidation products, insulin, glucagon and fasting blood glucose. Pancreas were isolated and stained with hematoxylin and eosin (HE), histoimmunological and morphometric factors were studied. The results of this study showed that Propolis was able to reduce blood glucose significantly compared with the diabetic untreated group. Hypercellularity and density of B cells increased in pancreatic tissue, islets size and percent of B cells increased significantly in Propolis treated group which may signify regeneration of islets or B cells in Propolis treated rats. In the current study, we have demonstrated that, both structural and functional improvements of pancreas. Further researches are highly needed to clarify the specific molecular and cellular targets of various constituents of Propolis.

Insulin Solution Stability and Biocompatibility with Materials Used for an Implantable Insulin Delivery Device Using Reverse Phase HPLC Methods

Insulin (Humulin® R IU500) has been delivered from an implantable artificial pancreas in diabetic rats and pigs. The artificial pancreas which was implanted in the peritoneum was fabricated from several biocompatible materials such as polycarbonate, stainless steel, polyurethane, titanium and a polyurethane resin. The device also contains a glucose responsive smart gel which controls the diffusion of insulin dependent on the surrounding glucose environment. As the insulin reservoir is refillable and in contact with the device materials, assessing its biocompatibility with these various device component materials was conducted. Insulin can undergo chemical degradation mainly via a deamidation reaction on glutamine and asparagine residues rendering its biological hormone functionality. Two Reverse Phase High Performance Liquid Chromatography (RP-HPLC) methods were developed and validated for detection of insulin and degradant Asn A21 desamido insulin (method A) and insulin and degradant Asn B3 desamido insulin (method B). Material biocompatibility studies show that stainless steel and titanium are suitable for an implantable insulin delivery device design over a 31-day period. The use of polycarbonate and polyurethane could be considered if the insulin reservoir in the device was only to remain in the device for less than 11 days after which time there is a loss in cresol which acts in a protective capacity for insulin stability.

Antidiabetic, Antihyperlipidemic, Antioxidant, Anti-inflammatory Activities of Ethanolic Seed Extract of Annona reticulata L. in Streptozotocin Induced Diabetic Rats.

Annona reticulata L. (Bullock's heart) is a pantropic tree commonly known as custard apple, which is used therapeutically for a variety of maladies. The present research was carried out to evaluate the possible protective effects of Annona reticulata L. (A. reticulata) ethanolic seed extract on an experimentally induced type 2 diabetes rat model. Male Albino Wistar rats were randomly divided into five groups with six animals in each group viz., control rats in group I, diabetic rats in group II, diabetic rats with 50 and 100 mg/kg/bw of ethanolic seed extract of A. reticulata in groups III and IV, respectively, and diabetic rats with metformin in group V. Treatment was given for 42 consecutive days through oral route by oro-gastric gavage. Administration of A. reticulata seed extract to diabetes rats significantly restored the alterations in the levels of body weight, food and water intake, fasting blood glucose (FBG), insulin levels, insulin sensitivity, HbA1c, HOMA-IR, islet area and insulin positive cells. Furthermore, A. reticulata significantly decreased the levels of triglycerides, cholesterol, LDL, and significantly increased the HDL in diabetic rats. A. reticulata effectively ameliorated the enzymatic (ALT, AST, ALP, GGT) and modification of histopathological changes in diabetic rats. The serum levels of the BUN, creatinine levels, uric acid, urine volume, and urinary protein were significantly declined with a significant elevation in CCr in diabetic rats treated with A. reticulata. MDA and NO levels were significantly reduced with an enhancement in SOD, CAT, and GPx antioxidant enzyme activities in the kidney, liver, and pancreas of diabetic rats treated with A. reticulata. Diabetic rats treated with A. reticulata have shown up-regulation in mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), Heme oxygenase-1 (HO-1) and protein expression level of Nrf2 with diminution in Keap1 mRNA expression level in pancreas, kidney, and liver. From the outcome of the current results, it can be inferred that seed extract of A. reticulata exhibits a protective effect in diabetic rats through its anti-diabetic, anti-hyperlipidemic, antioxidant and anti-inflammatory effects and could be considered as a promising treatment therapy in the treatment of diabetes mellitus.

A Study on Insulin Levels and the Expression of Glut 4in Streptozotocin (STZ) Induced Diabetic Rats Treated with Mustard Oil Diet.

The study was undertaken to evaluate the therapeutic effect of mustard oil incorporated diet in streptozotocin (STZ)-induced type 1 diabetic rats. Dietary composition has shown to play a significant role in improving insulin sensitivity. Various authors have reported the hypoglycemic effect of mustard oil in experimentally induced diabetic rats. In the present study,reverse transcriptase polymerase chain reaction (RT-PCR) was done to analyze the Glut 4 expression in STZ induced diabetic rats as it is a key player in glucose homeostasis. The effect of mustard oil on serum biochemical parameter and insulin levels was also studied. Twenty-four male Wistar rats were randomly divided into three different groups with each containing eight animals. The first, second and third groups were control, diabetic control and treatment group with mustard oil respectively. All the rats in respective groups were fed for 60days with iso-caloric mash diet containing 8% lipid. Diabetes was induced by intra-peritoneal administration of STZ (40mg/kg body weight). A highly significant reduction in blood glucose level, with an increase in insulin activity was observed in mustard oil-treated diabetic rats when compared to control group indicating anti-hyperglycemic activity of mustard oil. Mustard oil-treated diabetic rats showed increased expression of Glut 4 in muscle tissue when compared to diabetic control. A significant reduction in the levels of triacylglycerols, total cholesterol, VLDL and LDL and raised plasma HDL were noticed in mustard oil-treated diabetic rats when compared to diabetic control rats. Histopathological studies revealed a mild regeneration of β cells of pancreas in mustard oil-treated diabetic rats. The results from our investigation suggest that mustard oil elicits hypoglycemic effect by increased insulin activity and up-regulation of Glut 4 gene expression in muscle tissue of STZ-induced diabetic rats.

A sea cucumber (Holothuria leucospilota) polysaccharide improves the gut microbiome to alleviate the symptoms of type 2 diabetes mellitus in Goto-Kakizaki rats

Diabetes mellitus has become a worldwide concern in recent years. In this study, the effect of Holothuria leucospilota polysaccharide (HLP) on type 2 diabetes mellitus (T2DM) was investigated in Goto-Kakizaki (GK) rats. The results showed that HLP significantly improved glucose intolerance and regulated blood lipid and hormone levels (p < 0.05). Pathological analysis showed that HLP repaired the impairments of the pancreas and colon in diabetic rats. In addition, a high dose of HLP (200 mg/kg) significantly upregulated the gene expression of peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/AKT), glucose transporter-4 (GLUT4) and anti-apoptotic (Bcl-2), and downregulated the mRNA levels of pro-apoptotic (Bax) and cluster of differentiation 36 (CD36) in diabetic rats (p < 0.05). Furthermore, HLP treatment increased the short-chain fatty acid-producing bacteria and decreased the opportunistic bacterial pathogen in the feces of diabetic rats. These results demonstrated that HLP has the potential to ameliorate T2DM in GK rats.

β-cell Regenerative Potential of Selected Herbal Extracts in Alloxan Induced Diabetic Rats.

Effective β-cell regeneration is a recognized therapeutic strategy in the treatment of type 1 diabetes mellitus. Regeneration of β-cells could be achieved via exogenous natural sources as medicinal plant extracts. Medicinal plants selected for the investigation were Spondias pinnata (Linn. f.) Kurz, Coccinia grandis (L.) Voigt and Gmelina arborea Roxb. The objective was to determine the β-cell regenerative potential of these plant extracts in alloxan-induced diabetic rats. Alloxan monohydrate was used to induce diabetes (150 mg/kg, ip). Wistar albino rats were divided into six groups (n=6); healthy untreated rats (healthy control), alloxan-induced diabetic untreated rats (diabetic control), diabetic rats received the extracts (treatment groups) of S. pinnata (1.0 g/kg), C. grandis (0.75 g/kg), G. arobrea (1.00 g/kg) and diabetic rats received glibenclamide (0.5 mg/kg; positive control). The above treatment was continued for 30 days. On the 30th day, the rats were sacrificed and biochemical parameters were determined. In addition, histopathology and immunohistochemistry on the pancreatic tissue were done on the 30th day. According to the results obtained for biochemical parameters, there was a significant increase in the concentrations of serum insulin and C-peptide in plant extracts treated diabetic rats (p < 0.05). The extract of C. grandis produced the highest degree of β-cell regeneration demonstrated through an increase in the number of islets and percentage of the insulin-secreting β-cells (75%) in the pancreas of diabetic rats (p < 0.05) based on the histopathology and immunohistochemistry findings. The results revealed that the selected extracts of C. grandis (0.75 g/kg), G. arborea (1.00 g/kg) and S. pinnata (1.00 g/kg) exerted β-cell regenerative potential in diabetic rats. The three plant extracts would be valued as natural agents of prompting the β-cell regeneration in vivo.

Myrtenal attenuates oxidative stress and inflammation in a rat model of streptozotocin-induced diabetes

The present study was aimed to investigate the effect of myrtenal on diabetes-associated oxidative stress, lipid peroxidation (LPO), and inflammation using a rat model of streptozotocin (STZ)-induced diabetes. Following the induction of diabetes in male Wistar rats using STZ (40 mg/kg body weight), myrtenal (80 mg/kg body weight) was administered orally to diabetic rats for four weeks and then sacrificed to harvest tissues. We measured the levels of antioxidants, LPO, and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and the p65 subunit of nuclear factor-kappa B (NF-kB p65). Diabetic rats revealed increased levels of LPO, proinflammatory cytokines, and NF-kB p65, and decreased levels of antioxidants in the liver and pancreas. Supplementation with myrtenal significantly attenuated the diabetes-induced changes in the liver and pancreas of diabetic rats. Our findings suggest that myrtenal may serve as an antioxidant and anti-inflammatory agent against diabetes-associated oxidative stress and inflammation. Highlights Oral administration of myrtenal improved the antioxidant status in the liver and pancreas of diabetic rats. Myrtenal treatment diminished inflammation in the liver and pancreas of diabetic rats. Myrtenal supplementation averts oxidative stress and inflammation in diabetic rats. Myrtenal could serve as a potent antioxidant and anti-inflammatory agent in the management of diabetes.

Hesperidin ameliorates pancreatic β-cell dysfunction and apoptosis in streptozotocin-induced diabetic rat model

AimsThe current study was conducted to investigate the potential protective effects of hesperidin and its possible mechanisms of action on pancreatic β-cells in diabetes. Main methodsMale Sprague Dawley rats were made diabetic using 65 mg/kg intraperitoneal injection of streptozotocin, and then administered daily with 100 mg/kg of hesperidin over 4 weeks. On conclusion of the experiment, blood and pancreatic tissue were collected to determine the function of β-cells, apoptosis, oxidative stress, ER stress, and inflammation. Key findingsTreatment of diabetic rats with hesperidin, significantly decreased fasting blood glucose and food intake, along with increased body weight, serum and pancreatic insulin levels, and pancreatic-duodenal homeobox-1 (PDX-1) protein expression. The beneficial roles of hesperidin on diabetic pancreatic β-cells exhibited an increment in antioxidant SOD and GPx activities, and a decrement in nitrotyrosine as well as malondialdehyde (MDA) levels. Additionally, the elevated concentration of TNF-α and expressions of ER stress maker GRP78 and CHOP proteins in the pancreas of diabetic rats were significantly diminished by hesperidin treatment. Furthermore, hesperidin effectively modulated expressions of apoptosis-regulatory proteins in diabetic rat pancreas, as revealed by upregulating anti-apoptotic Bcl-xL; with a concomitant downregulating pro-apoptotic Bax, cleaved caspase-3, and inhibiting the activation of DNA repair protein poly (ADP-ribose) polymerase (PARP). SignificanceCollectively, these findings suggest that hesperidin may have the potential to protect pancreatic β-cells and improve their function by suppressing oxidative and ER stress, along with activating its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Antioxidant Activity of Hydro-Ethanolic Extract of Blighia sapida Stem Bark in the Pancreas of Alloxan-Induced Diabetic Rats

Blighia sapida is a plant belonging to the family of sapindaceae. In this study we aimed at investigating the possible antioxidant activities of hydro-ethanolic extract of Blighia sapida stem bark in the pancreas of alloxan-induced diabetic rats. Administration of the extract at 100mg/kg body weight significantly (P&lt;0.05) increased the activities of antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase in the pancreas of diabetic rats. Also the concentration of reduced glutathione increased in the pancreatic tissues of the diabetic rats while the levels of malondialdehyde and protein carbonyl generally decreased in the pancreas of alloxan-induced diabetic rats during the course of the experiment. These are indications of antioxidant properties of the stem bark of Blighia sapida with 100mg/kg body weight of the hydro-ethanolic extract showing good antioxidant activities by comparing favourably well with metformin, a standard antidiabetic drug. Keywords : Blighia sapida , diabetes mellitus, antioxidants, antioxidant enzymes DOI : 10.7176/JBAH/9-16-03 Publication date : August 31 st 2019

Antidiabetic effects of pterostilbene through PI3K/Akt signal pathway in high fat diet and STZ-induced diabetic rats

Pterostilbene (PTE) is a natural dimethylated analog of resveratrol, which exerts antioxidative, hypolipidemic and hypoglycemic effects; however, the underlying mechanism is not yet clear. In this study, we evaluated the effects of PTE on diabetic rats and clarified the underlying mechanism. Diabetes was induced in rats by streptozotocin (STZ) and a high-sugar and high-fat diet. Rats were then treated with PTE (20, 40 and 80 mg/kg/d) for 8 weeks. Oral glucose tolerance test (OGTT) was performed to measure the glycometabolism of the diabetic rats at the end of the treatment. Fasting blood glucose (FBG), fasting insulin (FINS) and lipid profile were determined using an automatic biochemistry analyzer and serum inflammatory factors were analyzed by enzyme-linked immunosorbent assay. Serum superoxide dismutase (SOD) and malondialdehyde (MDA) were also analyzed by spectrophotometry to evaluate the anti-oxidant effects. The expression of proteins of PPARγ and PI3K/Akt signaling pathway related proteins in adipose tissue of the diabetic rats was analyzed by Western blotting. PTE treatment significantly reduced weight loss, FBG, insulin resistance, serum lipid levels and inflammatory factors. PTE treatment also inhibited oxidative stress by decreasing MDA expression and increasing SOD expression. Simultaneously, PTE treatment significantly ameliorated morphological impairment of the pancreas in diabetic rats. Furthermore, PTE treatment significantly increased the protein expression of PPARγ, PI3K, p-Akt, GLUT4 and IRS-1 in adipose tissues of diabetic rats. This study suggests that PTE can exert antidiabetic effects via the PI3K/Akt signaling pathway.

Protective effect of theaflavin on glycoprotein components and TCA cycle enzymes in high-fat diet and streptozotocin-induced diabetic rats

BackgroundTheaflavins are major polyphenols in black tea which is the most widely consumed tea in the world. They possess a broad spectrum of biological activities, such as antioxidant, anti-tumor, anti-inflammatory, and cardio-protective effects. The present study was aimed to evaluate the protective effect of theaflavin on glycoprotein content and tricorboxylic acid cycle enzymes in high-fat diet and streptozotocin-induced diabetic rats as there was no study on this aspect. Diabetes was induced in male albino Wistar rats by feeding them with high-fat diet and injecting them intraperitoneally with streptozotocin (40 mg/kg b.wt).ResultsDifferent doses of theaflavin (25, 50, and 100 mg/kg b.wt /day) were administered orally to high-fat diet and streptozotocin-induced diabetic rats for 30 days for fixing the glucose lowering dose. However, the dose at 100 mg/kg b.wt showed a significant reduction in the levels of plasma glucose and Homeostatic Model Assessment of Insulin Resistance with concomitant elevation of insulin when compared to the other two doses (25 and 50 mg/kg b.wt). Hence, 100 mg/kg b.wt was fixed as an effective dose and used for further analysis. Theaflavin administration restored the altered glycosylated hemoglobin, hemoglobin and glycoproteins (Hexose, hexosamine, fucose, and sialic acid) and TCA cycle enzymes (isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase) near the normal levels by correcting hyperglycemia. Improved histological changes were observed in the pancreas of diabetic rats upon treatment with theaflavin which supported the biochemicals investigated.ConclusionThe effect produced by the theaflavin on various parameters was comparable to that of metformin—a reference antidiabetic drug. These findings suggest that theaflavin can replace the commercial drugs which could lead to reduction in toxicity and side effect caused by the later as well as reduce the secondary completions.

Hibiscus sabdariffa renews pancreatic β-cells in experimental type 1 diabetic model rats

This study evaluated the antidiabetic potentials of flavonoid-rich aqueous fraction of methanolic extract of Hibiscus sabdariffa calyx (HSCE) on the pancreatic β-cells of experimental type I diabetic model rats. Type 1 diabetes mellitus was induced in Wistar rats by a single intraperitoneal injection of 80mg/kg b/w streptozotocin (STZ) dissolved in 0.1M citrate buffer (pH 6.3). The rats were divided into five groups (n=12) including normal control group, test group I, diabetic negative control, test group II, and diabetic positive control. The test groups received 1.75g/kg b/w of HSCE by gavage for 15 days. Animals were sacrificed; the splenic portion of their pancreas and serum were evaluated for histopathological and biochemical parameters respectively. The regenerative effects of the extract on STZ-diabetes β-cells damage was evident from the results of the histopathological analysis and the biochemical parameters evaluated in the serum. Reduced levels of glutathione, catalase and superoxide dismutase in the serum of diabetic rats were significantly improved in the H.sabdariffa-treated rats (P<0.05). Histological examination of pancreatic islet sections revealed degenerative and necrotic changes (D) in the pancreatic islet of Langerhans, β-cell degranulation, pyknotic β-cell nuclei, decreased islet cellular density, and severe vacuolation (V) in the islet of STZ-diabetic negative control group. The morphology of the pancreas of HSCE-treated diabetic rats (test group II) revealed remarkable improvements in the islet of Langerhans. Stereological studies also revealed that HSCE-treatment remarkably improved volume of the pancreatic islets and the numerical density of β-cell (number of β-cells per unit area of islet) depleted by STZ diabetes. The study concluded that possible antidiabetic mechanism of Hibiscus sabdariffa in STZ diabetes is through induction of β-cell regeneration and its strong antioxidant potential.

Effects of Timolol Treatment on Pancreatic Antioxidant Enzymes in Streptozotocin-induced Diabetic Rats: An Experimental and Computational Study.

SummaryBackgroundThe study aimed to investigate whether timolol-treatment has a beneficial effect on pentose phosphate pathway enzyme activities such as glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGDH) enzyme activities and cAMP level in streptozotocin-induced diabetic rats in pancreatic tissuesMethodsDiabetes was induced by streptozotocin (STZ) in 3-month old male Wistar rats. The diabetic rats were treated with timolol (5 mg/kg body weight, for 12 weeks) while the control group received saline. Enzyme activities were determined in pancreas tissue. To support our results, we performed in silico calculations, using Protein Data Bank structures.ResultsTimolol treatment of STZ-induced diabetic rats had no noteworthy effect on high blood-glucose levels. However, this treatment induced activities of G6PD and 6PGDH in diabetic rats. Timolol treatment significantly increased cAMP level in diabetic pancreatic tissue. We found that timolol cannot bind strongly to either G6PD or 6PGD, but there is a relatively higher binding affinity to adenylyl cyclase, responsible for cAMP production, serving as a regulatory signal via specific cAMP-binding proteins.ConclusionsOur data point out that timolol treatment has beneficial effects on the antioxidant defence mechanism enzymes in the pancreas of STZ-induced diabetic rats.

Naringin Ameliorates Streptozotocin-Induced Diabetes through Forkhead Box M1-Mediated Beta Cell Proliferation

Background: Adult pancreatic beta cells, though quiescent, can proliferate in response to physiological need. This inherent character is used in exploring the possibilities of expanding the beta cell mass in the treatment of diabetes. Forkhead box M1 (FoxM1) transcription factor is an important regulator in the proliferation and survival of adult beta cell mass. Naringin, a flavanone glycoside, is reported to have antidiabetic activity and exhibited an increase in insulin levels in diabetic animals. Objectives: The present study tried to evaluate the role of naringin in the regulation of FoxM1 in the pancreas of diabetic rats and to reascertain its antilipidemic and antioxidant properties. Methods: Diabetes was induced in male rats using streptozotocin and treated with naringin (100 mg/kg) orally for 4 and 8 weeks. Serum biochemical parameters, insulin, gene and protein expression of FoxM1, and antioxidant markers in rat pancreas were analyzed. Results: Naringin administration reduced the blood sugar, urea, creatinine, and cholesterol values and improved the pancreatic antioxidant status in diabetic rats. Naringin-treated diabetic rats showed a significant increase in mRNA and protein expression of FoxM1 compared to the diabetic control rats, indicating regeneration of cells. It also increased the insulin immunopositive cells, indicating functional beta cells. Conclusion: Naringin was found to upregulate the FoxM1 transcription factor in diabetic animals, which influenced the proliferation and functional status of beta cells.

Flavonoid-Enriched Extract from Desert Plant Warionia saharae Improves Glucose and Cholesterol Levels in Diabetic Rats.

Background and Objective:Warionia saharae Benth and Coss, is a medicinal plant used for its anti-diabetic properties in Morocco. This study was designed to examine the effect of the Flavonoid-Enriched Extract (FEE) obtained from Warionia saharae (W. saharae) on glucose and lipid metabolism in normal and streptozotocin (STZ)-induced diabetic rats.Methods:Acute (6 h) and sub-chronic (15 days) oral administration of FEE (10 mg/kg) was used to assess the glucose and lipid-lowering activity in normal and diabetic rats. Furthermore, glucose test tolerance, liver histopathological examination and in vitro antioxidant activity of FEE were carried out in this study.Results:Results indicated that FEE was able to exert antihyperglycemic activity. Additionally, FEE improved histopathological status of liver and pancreas in diabetic rats and possessed antioxidant activity.Conclusion:In conclusion, the present investigation revealed that FEE had potent antidiabetic effect in diabetic rats.

Naringin (4′,5,7-Trihydroxyflavanone 7-Rhamnoglucoside) Attenuates β-Cell Dysfunction in Diabetic Rats through Upregulation of PDX-1

Background: Pancreatic duodenal homeobox-1 (PDX-1) is a key transcription factor which regulates Insulin gene expression and insulin secretion in adult β-cells and helps to maintain β-cells mass. Naringin, a flavanone, owing to its anti­oxidant property, is reported to have antidiabetic effects. Objectives: The present study tries to evaluate the role of naringin on the β-cell-specific transcription factor PDX-1 in diabetic rats. Methods: Diabetes was induced in male rats using streptozotocin and treated with naringin (100 mg/kg) orally for 4 and 8 weeks. Serum insulin level, Pdx-1 and Insulin gene expression, and PDX-1 protein expression were assessed in the rat pancreas. Histopathological and ultrastructural changes in the islet and β-cells were observed. Results: Naringin prevented leukocytic infiltration in the pancreas of diabetic rats and recouped the β-cells with adequate secretory granules. Naringin-treated diabetic rats showed significantly increased mRNA expression of Pdx-1 and Insulin genes, increased expression of transcription factor PDX-1, and higher serum insulin levels than the diabetic control animals. These changes were more pronounced in the 8-week naringin-treated diabetic animals. Conclusions: Naringin was found to be an effective antidiabetic agent which increased Insulin gene expression and insulin secretion by upregulating the PDX-1 gene and protein expression.

Lupenone is a good anti-inflammatory compound based on the network pharmacology.

The dried rhizome of Musa basjoo Sieb. et Zucc. is Rhizoma Musae. It has been used to treat diabetes in Miao medicine in China. Lupenone was isolated from Rhizoma Musae and has good anti-diabetic activity. Its mechanism of action is unclear. Diabetes is a chronic low-level systemic inflammatory disease, and lupenone has anti-inflammatory activity, but the underlying mechanism is not fully elucidated. In this study, we aimed to construct the drug-target biologic network and predict the anti-inflammatory mechanism of lupenone. The network-based pharmacologic analysis platform was used to identify the target proteins related to inflammation. Furthermore, the effects of lupenone on acute, subacute and diabetic pancreatic inflammation were evaluated. The "component-target-disease" network was constructed using Cytoscape. Lupenone could regulate transcription factor p65, NF-kappa-B inhibitor alpha, transcription factor AP-1, NF-kappa-B essential modulator, nuclear factor NF-kappa-B p105 subunit, epidermal growth factor receptor, hypoxia-inducible factor 1-alpha and other proteins related to the PI3K-Akt, Toll-like receptor and NF-kappa B signaling pathways. In addition, lupenone significantly decreased acute and subacute inflammation in mice as well as the IL-1β and IFN-γ levels in the pancreas of diabetic rats. The above results provide strong support for studying the molecular mechanism of lupenone in the treatment of diabetes from the perspective of anti-inflammation.

The Influence of Ethanolic Root Extracts of Ruellia tuberosa L. on Pancreatic Protease Activity and MDA Level of Rats (Rattus norvegicus) Induced by MLD-STZ

Diabetes mellitus (DM) is a metabolism disorder, indicated by increasing of blood glucose levels, due to lack of insulin secretion or insulin resistance. This study aimed to determine the influence of ethanolic root extracts of Ruellia tuberosa L on protease activity and MDA levels on pancreatic diabetic rats. This experiment used 20 rats in randomized design, that were divided into five groups: negative control, positive control, and three groups of treatments, with doses of 250, 375, and 500 mg/kg bw, respectively for 21 days. The positive control group and therapeutic group were induced by MLD-STZ (multiple-low dose streptozotocin) at dose of 20 mg/kg bw for 5 consecutive days, in order to induce diabetic states. Protease activity and MDA levels were determined by spectrophotometric method. The results showed that ethanolic root extracts of Ruellia tuberosa L. at dose of 250 mg/kg bw was the best dose to decrease significantly protease activity and MDA level in the pancreas of diabetic rats with the percentages of 52.11% and 50.54%, respectively.