Pancreas Of Diabetic Rats Research Articles

Transplantation of mesenchymal stem cells improves type 1 diabetes mellitus.

Bone-marrow-derived stem cells can regenerate pancreatic tissue in a model of type 1 diabetes mellitus. Mesenchymal stem cells (MSCs) form the main part of bone marrow. We show that the intrapancreatic transplantation of MSCs elevates serum insulin and C-peptide, while decreasing blood glucose. MSCs engrafted into the damaged rat pancreas become distributed into the blood vessels, acini, ducts, and islets. Renascent islets, islet-like clusters, and a small number of MSCs expressing insulin protein have been observed in the pancreas of diabetic rats. Intrapancreatic transplantation of MSCs triggers a series of molecular and cellular events, including differentiation towards the pancreas directly and the provision of a niche to start endogenous pancreatic regeneration, which ameliorates hypoinsulinemia and hyperglycemia caused by streptozotocin. These data establish the many roles of MSCs in the restoration of the function of an injured organ.

Protective effects of Egyptian cloudy apple juice and apple peel extract on lipid peroxidation, antioxidant enzymes and inflammatory status in diabetic rat pancreas.

BackgroundApples possess rich content of varied polyphenolic compounds showing a variety of biological activities that may ascribe to worthy effects against some chronic diseases. The present study was designed to assess the protective effects of the cloudy apple juice (CAJ) and apple peel extract (APE) of Egyptian Anna apple on the complications in experimental diabetes.Materials and methodsFour groups were studied. Diabetes was induced by a single dose of streptozotocin (STZ) to only three groups of albino Wistar rats. Two of the diabetic groups received either CAJ or APE for 21 days. At the end of the study, lipid profile parameters were measured in serum while lipid peroxidation (LPO) level, antioxidant enzyme activities and inflammatory markers were evaluated in pancreas tissue samples. The gas chromatography–mass spectrometry (GC-MS) analysis of phenolic compounds found in CAJ and APE was carried out. Moreover, total phenolic content of CAJ and APE were measured.ResultsThe significant increase of blood glucose level, serum total cholesterol (TC), triglycerides (TG), low- density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein (VLDL) levels, in addition to tissue malondialdehyde (MDA), nuclear factor kappa B (NF-kB), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8) levels, but a significant decrease in high-density lipoprotein cholesterol (HDL-C), and the activity of pancreatic antioxidant enzymes were the remarkably parameters observed in diabetic control rats. Dissimilarly, oral supplementation of 15 ml/kg CAJ and 1 g/kg APE for 21 days resulted in a significant decrease in fasting blood glucose, serum TC, TG, LDL-C, VLDL-C and tissue MDA, NF-kB, TNF-α, IL-6, IL-8 levels coupled with a significant elevation of HDL-C and antioxidant enzymes’ activity when compared with diabetic control animals.ConclusionsThe results indicate that Egyptian CAJ and APE supplementation may have protective effects against deleterious complications of diabetes mellitus.

Antioxidant treatment ameliorates experimental diabetes-induced depressive-like behaviour and reduces oxidative stress in brain and pancreas.

Studies have shown a relationship between diabetes mellitus (DM) and the development of major depressive disorder. Alterations in oxidative stress are associated with the pathophysiology of both diabetes mellitus and major depressive disorder. This study aimed to evaluate the effects of antioxidants N-acetylcysteine and deferoxamine on behaviour and oxidative stress parameters in diabetic rats. To this aim, after induction of diabetes by a single dose of alloxan, Wistar rats were treated with N-acetylcysteine or deferoxamine for 14 days, and then depressive-like behaviour was evaluated. Oxidative stress parameters were assessed in the prefrontal cortex, hippocampus, amygdala, nucleus accumbens and pancreas. Diabetic rats displayed depressive-like behaviour, and treatment with N-acetylcysteine reversed this alteration. Carbonyl protein levels were increased in the prefrontal cortex, hippocampus and pancreas of diabetic rats, and both N-acetylcysteine and deferoxamine reversed these alterations. Lipid damage was increased in the prefrontal cortex, hippocampus, amygdala and pancreas; however, treatment with N-acetylcysteine or deferoxamine reversed lipid damage only in the hippocampus and pancreas. Superoxide dismutase activity was decreased in the amygdala, nucleus accumbens and pancreas of diabetic rats. In diabetic rats, there was a decrease in catalase enzyme activity in the prefrontal cortex, amygdala, nucleus accumbens and pancreas, but an increase in the hippocampus. Treatment with antioxidants did not have an effect on the activity of antioxidant enzymes. In conclusion, animal model of diabetes produced depressive-like behaviour and oxidative stress in the brain and periphery. Treatment with antioxidants could be a viable alternative to treat behavioural and biochemical alterations induced by diabetes.

Inhibitory effects of Cymodocea nodosa sulphated polysaccharide on α-amylase activity, liver-kidney toxicities and lipid profile disorders in diabetic rats

This study aimed to evaluate for the first time the effects of Cymodocea nodosa sulphated polysaccharide (CNSP) on the α-amylase activity, hyperglycaemia, liver-kidney functions, and pancreatic architecture of alloxan-induced diabetic rats. Animals were allocated into four groups of seven rats each, the body weight and blood glucose levels were estimated periodically for 2 months of treatment by gastric gavages route. The CNSP effect was confirmed by biochemical procedures and histological study. The inhibition of α-amylase activity and protection of pancreatic β-cells induced a decrease in the blood glucose levels and regulated the lipid profile in the plasma of the treated diabetic rats, which helped to maintain the homeostasis of blood lipid. Moreover, CNSP administration induced a significant decrease in the levels of lipid peroxidation in the pancreas, liver and kidney of diabetic rats and protects their functions attested by a decrease in the levels of toxicity parameters in blood.

Ameliorative effect of Myristica fragrans (nutmeg) extract on oxidative status and histology of pancreas in alloxan induced diabetic rats.

Many traditional treatments have been recommended in the alternative system of medicine for the treatment of diabetes mellitus. The aim of this study was to assess oxidative stress and histological changes in the pancreas of alloxan-induced diabetic rats following Myristica fragrans seed (nutmeg) extract treatment. Forty-eight male Wistar rats weighing 200-250 g were randomly divided into six groups of 8 rats each - group I, non-diabetic rats; group II, diabetic rats; groups III, IV and V, diabetic rats given orally nutmeg extract at levels of 50, 100 and 200 mg/kg, respectively; and group VI, diabetic rats given orally metformin (100 mg/kg). The experiment lasted for 28 days. Data showed that nutmeg extract (100 and 200 mg/kg) significantly decreased the blood glucose levels and increased the levels of serum insulin in diabetic rats. Administration of nutmeg extract to diabetic rats reduced oxidative stress and improved the antioxidant activities in pancreatic tissue. Histopathologic results of treated groups revealed marked improvement in the morphology of the pancreas compared with the control diabetic group. In addition, number of pancreatic islets and per cent of β-cells increased significantly in these groups in comparison with diabetic untreated group. These results suggest that nutmeg extract has potent antidiabetic and β-cell protection activities in alloxan induced diabetic rats, possibly via its antioxidant properties.

Flaxseed Protects Against Diabetes-Induced Glucotoxicity by Modulating Pentose Phosphate Pathway and Glutathione-Dependent Enzyme Activities in Rats

ABSTRACTThis study investigated the effects of flaxseed (Linum usitatissimum L.) intake on general metabolism, pentose phosphate pathway (PPP) and glutathione-dependent enzymes in diabetic rats. Diabetes was induced by streptozotocin injection (40 mg/kg, i.p.) and the enzyme activities were determined spectrophotometrically. Diabetic and control rats were divided in two subgroups, one untreated, and one treated with flaxseed (0.714 g/kg body weight/day; orally) for 12 weeks. Flaxseed ameliorated decreased body weight (p < .05) and increased blood glucose (p < .001), triglyceride (p < .001), ALT (p < .001) and AST (p < .001) in diabetic rats. Diabetes resulted in increased glucose-6-phosphate dehydrogenase (G6PD) (p < .05) and decreased glutathione-S-transferase (GST) (p < .01), but unchanged 6-phosphogluconate dehydrogenase (6PGD) and glutathione reductase (GR) in the brain of rats. These alterations were partially improved by flaxseed in comparison to diabetic untreated group (p < .05). G6PD, 6PGD, GR were elevated (p < .001), while GST unchanged in the lung of diabetic untreated group compared to control. Flaxseed partially prevented the increase in 6PGD (p < .05) and GR (p < .01), but unaffected G6PD in the lung of diabetic rats. G6PD (p < .001), 6PGD (p < .05), GR (p < .001) were augmented, while GST showed a significant (p < .001) depletion in the pancreas of diabetic untreated rats compared to control. Diabetic alterations observed in pancreatic enzyme activities were significantly prevented by flaxseed. Furthermore, a remarkable decrease in 6PGD (p < .001) and an increase in G6PD (threefold of control) were found in the lens of diabetic untreated group that were completely prevented by flaxseed (p < .001). Flaxseed has beneficial effects against diabetes-induced glucotoxicity by modulating G6PD, 6PGD, GR and GST activities in tissues.

Curcumin pretreatment mediates antidiabetogenesis via functional regulation of adrenergic receptor subtypes in the pancreas of multiple low-dose streptozotocin-induced diabetic rats

Lifestyle modification pivoting on nutritional management holds tremendous potential to meet the challenge of management of diabetes. The current study hypothesizes that regular uptake of curcumin lowers the incidence of diabetes by functional regulation of pancreatic adrenergic receptor subtypes. The specific objective of the study was to identify the regulatory pathways implicated in the antidiabetogenesis effect of curcumin in multiple low-dose streptozotocin (MLD-STZ)-induced diabetic Wistar rats. Administration of MLD-STZ to curcumin-pretreated rats induced a prediabetic condition. Scatchard analysis, real-time polymerase chain reaction, and confocal microscopic studies confirmed a significant increase in α2-adrenergic receptor expression in the pancreas of diabetic rats. Pretreatment with curcumin significantly decreased α2-adrenergic receptor expression. The diabetic group showed a significant decrease in the expression of β-adrenergic receptors when compared with control. Pretreatment significantly increased β-adrenergic receptor expression to near control. When compared with the diabetic rats, a significant up-regulation of CREB, phospholipase C, insulin receptor, and glucose transporter 2 were observed in the pretreated group. Curcumin pretreatment was also able to maintain near control levels of cyclic adenosine monophosphate, cyclic guanosine monophosphate, and inositol triphosphate. These results indicate that a marked decline in α2-adrenergic receptor function relents sympathetic inhibition of insulin release. It also follows that escalated signaling through β-adrenergic receptors mediates neuronal stimulation of hyperglycemia-induced β-cell compensatory response. Curcumin-mediated functional regulation of adrenergic receptors and modulation of key cell signaling molecules improve pancreatic glucose sensing, insulin gene expression, and insulin secretion.

Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats.

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels.

Hypoglycemic and antioxidant activities of Caesalpinia ferrea Martius leaf extract in streptozotocin-induced diabetic rats

ObjectiveTo evaluate the antidiabetic and antioxidant effects of aqueous ethanolic extract of Caesalpinia ferrea (C. ferrea) leaf in normal and streptozotocin (STZ) induced diabetic rats. MethodsMale Sprague-Dawley rats divided into 6 groups of 6 rats each were assigned into diabetic and non-diabetic groups. Diabetes was induced in rats by single intraperitoneal administration of STZ (65 mg/kg body weight). C. ferrea extract at the doses of 250 and 500 mg/kg body weight was orally administered to both diabetic and non-diabetic animals for a period of 30 days. After completion of experimental duration serum, liver and pancreas were used for evaluating biochemical and histopathological changes. ResultsOral administration of C. ferrea leaf extract significantly reduced elevated serum glucose, α-amylase, liver function levels and significantly increased serum insulin, total protein and body weight as well as improved lipid profile due to diabetes. Furthermore, the treatment resulted in a marked increase in glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione, and diminished levels of lipid peroxidation in liver and pancreas of diabetic rats. Histopathological studies demonstrated the reduction in the pancreas and liver damage and confirmed the biochemical findings. ConclusionsFrom the present study, it can be concluded that the C. ferrea leaf extract effectively improved hyperglycaemia while inhibiting the progression of oxidative stress in STZ-induced diabetic rats. Hence, it can be used in the management of diabetes mellitus.

Haematologic profile and histomorphologic assessment of the pancreas and liver of alloxan-induced diabetic rats treated with graded concentration of quail egg

This study was designed to investigate the effect of quail egg on the haematological parameters and the histopathology changes of the pancreas and liver of alloxan-induced diabetic Wistar albino male rats. Thirty albino rats with a mean weight of 160 ± 15 g were randomly selected into five groups, each with six rats. Groups 2, 3, 4 and 5 were induced with diabetes by intraperitoneal injection of alloxan at a dose of 160 mg/kg. Upon confirmation of diabetes (fasting blood sugar (FBS) >126 mg/dl), rats in groups 2, 3 and 4 were orally administered with 30, 15 and 7.5 mg/ml of quail egg. Group 1 and 5 rats were administered with distilled water to serve as positive and negative controls, respectively. The treatment lasted for 21 days, and blood samples for haematology [red blood cell (RBC), white blood cell (WBC), haemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC)] analyses were collected on days 7, 14 and 21. On the 21st day, two rats per group were humanely sacrificed and the vital organs (pancreas and liver) were collected for histopathology. Haematologic results obtained showed marked reduction (p 0.05) in the WBC of the induced animals when compared with the positive control. However, on administration of the quail egg at 30 mg/ml, there was a significant increase (p 0.05). The histopathology of the pancreas of the untreated induced rats showed immense cytoplasmic vacuolation, while those treated with 30 mg/ml of quail egg showed mild cytoplasmic vacuolation. The liver histopathology of the untreated induced rats showed mononuclear leucocyte and multifocal areas of coagulative necrosis, while the rats treated with 30 mg/ml of quail egg showed no visible lesion. It can be concluded that quail egg possesses hepatoprotective property and also can improve haematologic profile of diabetic rats.

Magnetic resonance imaging of the pancreas in streptozotocin-induced diabetic rats: Gadofluorine P and Gd-DOTA.

To investigate the performance of Gadofluorine P-enhanced magnetic resonance imaging (MRI) on the diagnosis of diabetes in a streptozotocin (STZ) -induced diabetic rat model. Fischer 344 rats were treated with STZ. Rats not treated with STZ served as controls. T1-weighted MRI was performed using a 3T scanner before and after the injection of Gd-DOTA or Gadofluorine P (6 diabetic rats, 5 controls). The normalized signal intensity (SI) and the enhancement ratio (ER) of the pancreas were measured at each time point, and the values were compared between the normal and diabetic rats using the Mann-Whitney test. In addition, the values were correlated with the mean islet number. Optimal cut-off values were calculated using a positive test based on receiver operating characteristics. Intrapancreatic Gd concentration after the injection of each contrast media was measured using laser ablation-inductively coupled plasma-mass spectrometry in a separate set of rats (4 diabetic rats, 4 controls for Gadofluorine P; 2, 2 for Gd-DOTA). The normalized SI and ER of the pancreas using Gd-DOTA were not significantly different between diabetic rats and controls. With Gadofluorine P, the values were significantly higher in the diabetic rats than in the control rats 30 min after injection (P < 0.05). The area under the receiver operating characteristic curve that differentiated diabetic rats from the control group was greater for Gadofluorine P than for Gd-DOTA (0.967 vs 0.667, P = 0.085). An increase in normalized SI 30 min after Gadofluorine P was correlated with a decrease in the mean number of islets (r (2) = 0.510, P = 0.014). Intra-pancreatic Gd was higher in rats with Gadofluorine P injection than Gd-DOTA injection (Gadofluorine P vs Gd-DOTA, 7.37 vs 0.00, P < 0.01). A significant difference in the concentration of intrapancreatic Gd was observed between the control and diabetic animals that were sacrificed 30 min after Gadofluorine P injection (control vs diabetic, 3.25 ng/g vs 10.55 ng/g, P < 0.05) CONCLUSION: In this STZ-induced diabetes rat model, Gadofluorine P-enhanced MRI of the pancreas showed high accuracy in the diagnosis of diabetes.

Vitamin D3 supplementation increases insulin level by regulating altered IP3 and AMPA receptor expression in the pancreatic islets of streptozotocin-induced diabetic rat

Pancreatic islets, particularly insulin-secreting β cells, share common characteristics with neurons. Glutamate is one of the major excitatory neurotransmitter in the brain and pancreas, and its action is mediated through glutamate receptors. In the present work, we analysed the role of vitamin D3 in the modulation of AMPA receptor subunit and their functional role in insulin release. Radio receptor binding study in diabetic rats showed a significant increase in AMPA receptor density. Insulin AMPA colabelling study showed an altered AMPA GluR2 and GluR4 subunit expression in the pancreatic beta cells. We also found lowered IP3 content and decreased IP3 receptor in pancreas of diabetic rats. The alterations in AMPA and IP3 receptor resulted in reduced cytosolic calcium level concentration, which further blocks Ca2+-mediated insulin release. Vitamin D3 supplementation restored the alteration in vitamin D receptor expression, AMPA receptor density and AMPA and IP3 receptor expression in the pancreatic islets that helps to restore the calcium-mediated insulin secretion. Our study reveals the antidiabetic property of vitamin D3 that is suggested to have therapeutic role through regulating glutamatergic function in diabetic rats.

Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

Distribution of nociceptin in pancreatic islet cells of normal and diabetic rats.

Nociceptin has been reported to play an important role in the regulation of pancreatic exocrine secretion. Most of the studies performed on nociceptin are mainly physiological rather than morphological in nature. The present study investigated the pattern of distribution of nociceptin in the endocrine pancreas of normal and diabetic rats. Immunohistochemistry, immunofluorescence, Western blot, and double-labeled immunoelectron microscopy were used in this study. Diabetes was induced using streptozotocin (60 mg/kg body weight). Nociceptin-immunoreactive cells were observed in the central and peripheral regions of the islets of both normal and diabetic rat pancreas. The number of nociceptin-positive cells was significantly (P < 0.05) lower in the islet of diabetic rats compared with the control. Immunofluorescence study showed that nociceptin colocalizes with insulin in pancreatic β-cells. The degree of colocalization of nociceptin with insulin was severely deranged after the onset of diabetes. Moreover, immunogold particles conjugated with either nociceptin or insulin were observed on the granules of pancreatic β-cell. The number of nociceptin-labeled colloidal gold particles was significantly lower after the onset of diabetes. Nociceptin is present in pancreatic islets cells and colocalizes with insulin. Nociceptin may have a physiological role in the metabolism of insulin.

Novel Anti-Diabetic Formula: Recover Islet ?-Cell dysfunction with the implementation of molecular approach

The regulation of PPAR? and PPAR? at m-RNAs expression level is responsible for Islet ?-cell dysfunction and insulin secretion seen in diabetic rats. Many traditional treatments have been recommended in the alternative system of medicine for the treatment of diabetes mellitus. Stevia rebaudiana and Gurmmar is a nontoxic natural therapeutic agent revealed to own diuretic, hypotensive and hypoglycemic properties. The ground of this study was to examine the anti-hyperglycemic property, expression of m-RNA at PPAR? and PPAR? receptors and islet ?-cells dysfunction of a combined aqueous extracts of Stevia rebaudiana and Gurmmar is on streptozotocin induced diabetic wistar rats. The diabetes induced rats were fed with plant extracts at the increasing dosage of 200mg, 300mg and 500mg of body weight. The combined plant extracts administrated rats revealed a significantly (P&lt;0.001) rise of serum insulin levels and higher reduction in hyperglycemia or hyperlipidemia when compared to the diabetic control rats (P&lt;0.001) and also an increase the m-RNAs expansion of PPAR? and PPAR? respectively. The histological studies of the endocrine region of pancreas of diabetic rats revealed that shrinkage of ?-cells of islets of langerhans. The combined plant extracts treated rats revealed recovery of ?-cells. The recovery of ?-cells was evident at higher dose level i.e. 500mg/by wt extracts fed groups. According to the biochemical, molecular and histological results obtained, it was concluded that the combined plant extracts of this plant may sustain anti-diabetic properties by recovery Islet ?-cell dysfunction with the implementation of molecular approach.

Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a secoiridoid glycoside, prevents and protects streptozotocin-induced β-cell damage in Wistar rat pancreas.

Diabetes mellitus is globally the major cause for metabolic syndrome in STZ-induced diabetic rats, leading to mortality. Treatment of diabetes by oral hypoglycemic agents causes adverse side effects and thus treatment with natural herbal drugs like swertiamarin is promising. Swertiamarin, an active compound isolated from Enicostemma littorale possesses antidiabetic activity and enhances β cell regeneration which causes reversal of diabetes. The present study aims at the following: (1) to evaluate antidiabetic, anti-hyperlipidaemic, activity of swertiamarin in Streptozotocin- induced diabetic rats using biomarkers. (2) To assess histopathological alterations in Pancreas, Liver, Kidney, and Heart of swertiamarin-treated STZ-induced diabetic rats and confirm cytoprotective activity of swertiamarin by Immunohistochemistry and morphometric investigations. Diabetes was induced intraperitoneally in male Wistar rats by Streptozotocin (STZ 50mg/kg). After STZ-induction, hyperglycemic rats were treated with doses of swertiamarin orally (15, 25, 50mg/kg) each for 28days. Glibenclamide (2.5mg/kg), a sulphonyl urea, was used as a standard drug. The glycemic control was measured by the biochemical parameter assays. Histopathology analysis of organs and immunohistochemistry of islets were carried out. Our study results showed that oral administration of swertiamarin at a dosage of 15, 25, 50mg/kg bw for 28days resulted in a significant (p<0.01) decrease in fasting blood glucose, HbA1c, TC, TG, LDL, and increased the levels of hemoglobin, plasma insulin, TP, body weight, and HDL levels significantly (p<0.01) when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies. The effect of swertiamarin on Carbohydrate-metabolizing enzymes was investigated and found to have normal therapeutic activity. Histopathological studies of Pancreas of swertiamarin-treated diabetic rats showed regeneration of islets when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies. Our research results clearly substantiate that swertiamarin possesses antihyperglycemic, antihyperlipidemic, cytoprotective, and immune reactivity and also a broad spectrum potential of treating diabetes and other complications related to diabetes and hence can be developed into a potent oral antidiabetic drug.

Rosmarinic acid modulates the antioxidant status and protects pancreatic tissues from glucolipotoxicity mediated oxidative stress in high-fat diet: streptozotocin-induced diabetic rats.

Persistent hyperglycemia and elevated levels of free fatty acids (FFA) contribute to oxidative stress, a proximate cause for the onset and progression of diabetes and its complications. The present study was hypothesized to evaluate the anti-diabetic potential of Rosmarinic acid (RA) during high-fat diet (HFD)-streptozotocin (STZ)-induced type 2 Diabetes (T2D) in wistar albino rats. Oral administration of RA (100 mg/kg b.w) significantly (p < 0.05) increased the insulin sensitivity index (ISI0,120), while the levels of blood glucose, HbA1c, advanced glycation end products (AGE), TNF-α, IL-1β, IL 6, NO, p-JNK, P38 MAPK and NF-κB were significantly reduced, with a concomitant elevation in the plasma insulin levels in diabetic rats. Furthermore, RA treatment significantly (p < 0.05) reduced the levels of triglycerides, FFA and cholesterol in serum, and reduced the levels of lipid peroxides, AOPP's and protein carbonyls in the plasma and pancreas of diabetic rats. The diminished activities of pancreatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) and the decreased levels of plasma ceruloplasmin, vitamin C, vitamin E and reduced glutathione (GSH) in diabetic rats were also significantly (p < 0.05) recovered upon RA treatment denoting its antioxidant potential which was confirmed by Nrf-2, hemeoxyenase (HO-1) levels. Histological, ultrastructural and immunohistochemical data demonstrate that oral administration of RA protects pancreatic β-cells from oxidative niche in HFD-STZ-induced experimental diabetes. Our findings suggest that the oral treatment with RA alleviates pancreatic β-cell dysfunction and glucolipotoxicity-mediated oxidative stress during HFD-STZ-induced T2DM, perhaps through its antioxidant potential.

Antidiabetic and antidyslipidemic activities of aqueous leaf extract of Dioscoreophyllum cumminsii (Stapf) Diels in alloxan-induced diabetic rats

Ethnopharmacological relevanceDioscoreophyllum cumminsii (Stapf) Diels leaves are used in the management of diabetics in Nigeria. Thus, the antidiabetic activity of aqueous D. cumminsii leaf extract and its capability to halt oxidative stress and dyslipidemia in alloxan-induced diabetic rats was investigated. MethodologyAntidiabetic was evaluated in alloxan-induced diabetes rats. Diabetic rats were treated with 50, 100 and 200mg/kg body weight of the extract. ResultThe aqueous extract of D. cumminsii leaves significantly reduced blood glucose level in a dose dependent manner with highest dose producing 72% reduction after 21 days administration, which was compared significantly (P<0.05) with the control group and glibenclamide treated groups. Similarly, aqueous extract of D. cumminsii significantly reversed reduction in insulin in alloxan-induced diabetic rats. Alloxan-induced diabetic mediated alterations in liver and serum cholesterol, triacylglycerides, high-density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc) and very low-density lipoprotein cholesterol (VLDLc) were significantly (P<0.05) restored by the extract. Aqueous extract of D. cumminsii leaves significantly attenuated the decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase in the liver and pancreas of alloxan-induced diabetic rats. Elevation in the concentration of malondialdehyde was significantly (P<0.05) lowered by D. cumminsii leaves extract. The diabetic-mediated alteration in the architecture of liver was alleviated by the extract. ConclusionOverall, aqueous extract of D. cumminsii leaves at all doses investigated reduced blood glucose level and prevented oxidative stress and dyslipidemia in alloxan-induced diabetic rats.

Trans-anethole, a terpenoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats.

Trans-anethole (TA), a terpenoid and a principle constituent of many essential oils from medicinal plants possess hypoglycemic and antioxidant activities. This study was undertaken to explore beneficial effects of TA on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced type 2 diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40mg/kg BW). TA was administered to diabetic rats at a dose of 20, 40 and 80mg/kg BW for 45 days. However, the dose at 80mg/kg BW, resulted in a significant reduction in the levels of plasma glucose, glycosylated haemoglobin (HbA1c) and increase in the levels of insulin and haemoglobin (Hb). Upon administration of TA, the altered levels of liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase) and gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in the liver and kidney of diabetic rats significantly reverted to near normal levels. In addition to this, TA also improved the hepatic and muscle glycogen content in diabetic rats. The histological studies showed the ameliorative effect of TA on the β-cells of pancreas in diabetic rats. The results were compared with glibenclamide, a standard oral hypoglycemic drug. These encouraging findings suggest that TA may be used as a propitious bioactive compound in the development of therapeutic agents against type 2 diabetes mellitus.

Protective effect of polysaccharides from Opuntia dillenii Haw. fruits on streptozotocin-induced diabetic rats

In this study, a novel water-soluble polysaccharide fraction with molecular weight of 6479.1kDa was isolated from the fruits of Opuntia dillenii Haw., which consisted of rhamnose, xylose, mannose and glucose in the molar ratio of 14.99:1.14:1.00:6.47. The protective effect of O. dillenii Haw. fruits polysaccharide (ODFP) against oxidative damage in streptozotocin (STZ)-induced diabetic rats was investigated. The results showed that oral administration of ODFP significantly decreased food intake, water intake, urine production, organ weights and blood glucose level, and increased body weight in STZ-induced diabetic rats. ODFP also significantly increased the activities of SOD, GPx and CAT, and decreased malondialdehyde level in serum, liver, kidney, and pancreas in STZ-induced diabetic rats. Moreover, histopathological examination showed that ODFP could markedly improve the structure integrity of pancreatic islet tissue in STZ-induced diabetic rats. These results suggest that ODFP have hypoglycemic and antioxidant properties and can protect rats from STZ-induced oxidative damage.