Liver Of Streptozotocin-induced Diabetic Rats Research Articles

Effect of aminoguanidine on plasminogen activator inhibitor-1 and receptor of advanced glycation endproduct in the liver of streptozotocin-induced diabetic rats

Objectives: Advanced glycation end products (AGEs) play an important role in the development and progression of diabetic complications. The receptor for AGE (RAGE) is the ligand-binding site of AGE that initiates and accelerates the atherosclerotic process. Plasminogen activator inhibitor-1 (PAI-1) is a prothrombotic factor that has been proposed as a biological marker for prognostic assessment, monitoring of microvascular and macrovascular complications in diabetes. The purpose of this study is to investigate the effects of aminoguanidine on RAGE and PAI-1 expression levels in the liver of streptozotocin-induced diabetic rats.
 Methods: Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ, 50 mg/kg). On day 3, diabetic rats were administered 50, 100, and 200 mg/kg/day of aminoguanidine. The expression of PAI-1 and RAGE in the liver tissue was evaluated using real-time PCR.
 Results: PAI-1 and RAGE gene expression levels were higher in the liver of the diabetic rats compared to the control group. Aminoguanidine at 50, 100, and 200 mg/kg decreased PAI-1 and RAGE gene expression in the liver (p<0.001 at all doses). However, these genes were downregulated only at a dose of 200 mg/kg in healthy rats (p<0.0001). In addition, hepatic AGE protein levels were significantly decreased following treatment of the diabetic rats with aminoguanidine (p<0.001). There was also a significant correlation between AGE protein concentration and the expression of PAI-1 and RAGE.
 Conclusion: In summary, the data of the present study suggest that aminoguanidine reduced the expression of PAI-1 and RAGE in the liver of the diabetic rats.

An Ethyl Acetate Extract of Eryngium carlinae Inflorescences Attenuates Oxidative Stress and Inflammation in the Liver of Streptozotocin-Induced Diabetic Rats.

Secondary metabolites such as flavonoids are promising in the treatment of non-alcoholic fatty liver disease (NAFLD), which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated regarding their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from streptozotocin (STZ)-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver triacylglycerides (TG) levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. We hypothesize that solvent polarity and consequently chemical composition of the ethyl acetate extract of E. carlinae, exert the beneficial effects due to phenolic compounds. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.

Attenuation of the cytotoxic, nephrotoxic and hepatotoxic effects of streptozotocin-induced diabetic rats by aqueous extract of Lepidium sativum L. (Brassicaceae)

Diabetes mellitus is a health condition whose major feature is hyperglycemia that arises from various etiologies. Diabetes mellitus is connected with constraints in the metabolism of proteins and lipids which leads to complications such as hepatopathy, nephropathy, retinopathy and vasculopathy. Plant resources are utilized for better beneficial curative molecules, minimal side effects and cost. Lepidium sativum (garden cress) is a plant whose parts have been reportedly employed in the treatment of conditions like inflammation, diabetes, pyretism, hemorrhage and hypertension. This histopathological study sought to investigate the effect of the aqueous extract of L. sativum on the tissues of the pancreas, kidney, and liver in streptozotocin-induced diabetic rats. Haematoxylin and Eosin Staining method of histopathology was employed and the cytotoxic, nephrotoxic and hepatoxic effects on the pancreatic Islet cells, kidney and liver were attenuated on treatment with different doses of aqueous extracts of L. sativum plant.

The protective effects of vitamin D3 on histopathology of pancreas and liver in streptozotocin-induced diabetic rats

The protective effects of vitamin D3 on histopathology of pancreas and liver in streptozotocin-induced diabetic rats

Early initiation of insulin attenuates histological and functional changes in the liver of streptozotocin-induced diabetic rats using 99mTc-sulfur colloid functional imaging

This study aimed to investigate the effect of insulin on the reticuloendothelial system (RES) in the liver and spleen in diabetic rats. Sprague Dawley rats were divided into control, diabetic rats (DM) and diabetic rats treated with insulin (IDM) for 2 weeks. Rats were imaged with technetium-99m-sulfur colloid (99mTc-SC) tracer to determine regional distributions of the tracer for all groups by drawing regions of interest and then obtained the ratios as the cumulative counts of heart, liver, and spleen to the whole body (WB). Liver tissue from sacrificed rats from each group was examined by light and electron microscopy. 99mTc-SC uptake ratios showed a lower liver to WB uptake ratio in the DM rats compared to both controls and IDM rats. Electron microscopy showed severe vacuolization of the hepatocytes of DM rats. The IDM rats show complete resolution of the vacuolization. The early administration of insulin for 2 weeks to diabetic rats could significantly resolve the phagocytic RES function and histological changes in the liver.

Ameliorative effects of garlic oil on FNDC5 and irisin sensitivity in liver of streptozotocin-induced diabetic rats.

This study was aimed to investigate the effects of garlic oil (GO), an important natural constituent used in alleviating diabetes and its complications, on the expression levels of irisin and related genes. Thirty-two rats were divided into four groups: Control, Diabetes-Control, Diabetes+GO 100 mg/kg/day and Control+GO 100 mg/kg/day for 45 days. The measurements included: changes in liver Peroxisome proliferator-activated receptor-gamma-coactivator (PGC)-1α, Fibronectin Type-III-Domain-Containing5 (FNDC5), irisin expression, mRNA expression of p38 and TNF-α (Tumour necrosis factor-α), total-antioxidant-status (L-TAS; S-TAS), total-oxidant-status (L-TOS; S-TOS) in liver and serum, respectively. There was a significant reduction in serum levels of irisin and S-TAS and expression of PGC-1α and FNDC5 in liver in Diabetes-control compared to Control-group, while a significant increase in serum levels of fasting blood glucose (FBG) and TOS, also p38 and TNF-α expressions in liver. In Diabetes+GO group, there was a significant increase in serum irisin and S-TAS, also expression of PGC-1α and FNDC5 in liver, while serum FBG, S-TOS levels, and mRNA expression of p38 and TNF-α in liver were decreased compared to Diabetes-control group (P < 0.05). GO alleviated the diabetic liver injury by decreasing Oxidative-Stress parameters and regulation PGC-lα, FNDC5, irisin and P38, keeping the balance of TAS/TOS and TNF-α.

Effects of black cumin seed oil on oxidative stress and expression of membrane-cytoskeleton linker proteins, radixin, and moesin in streptozotocin-induced diabetic rat liver.

Background and Aim:This study examined the effects of black cumin seed oil treatment on oxidative stress and the expression of radixin and moesin in the liver of experimental diabetic rats.Materials and Methods:Eighteen rats were divided into 3 equal groups (control, diabetes, treatment). The control group was not exposed to any experimental treatment. Streptozotocin was administered to the rats in the diabetes and treatment groups. A 2.5 mL/kg dose of black cumin seed oil was administered daily for 56 days to the treatment group. At the conclusion of the experiment, the blood level of malondialdehyde (MDA) and glutathione (GSH) was measured. The expression level and the cellular distribution of radixin and moesin in the liver were analyzed.Results:The plasma MDA (3.05±0.45 nmol/mL) and GSH (78.49±20.45 μmol/L) levels in the diabetes group were significantly different (p<0.01) from the levels observed in the control group (MDA: 1.09±0.31 nmol/mL, GSH: 277.29±17.02 μmol/L) and the treatment group (MDA: 1.40±0.53 nmol/mL, GSH: 132.22±11.81 μmol/L). Immunohistochemistry and western blotting analyses indicated that while the level of radixin was not significantly between the groups (p>0.05) and moesin expression was significantly downregulated (p<0.05) in the experimental group, the treatment was ineffective.Conclusion:The administered dose was sufficient to prevent oxidative stress, but was not sufficient to alleviate the effects of diabetes on moesin expression in hepatic sinusoidal cells.

Protective effects of a standardized extract of Iris germanica on pancreas and liver in streptozotocin-induced diabetic rats.

Background and purpose:Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of Iris germanica. The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of Iris germanica rhizomes on streptozotocin-induced diabetic rats.Experimental approach:Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the Iris germanica extract (IGE).Findings/Results:Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level.Conclusion and implication:These findings suggest that Iris germanica rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.

Syringic acid improves oxidative stress and mitochondrial biogenesis in the liver of streptozotocin-induced diabetic rats

Objective: To determine the effects of syringic acid on hepatic damage in diabetic rats.Methods: Diabetes was induced by streptozotocin. Diabetic rats were given syringic acid at doses of 25, 50 and 100 mg/kg by oral gavage for 6 weeks. Syringic acid effects on the liver were evaluated by examination of plasma biochemical parameters, and pathological study. In addition, biomarkers of lipid peroxidation and antioxidant status of liver tissues were assessed. Real time-PCR was performed to investigate the mRNA expression levels of mitochondrial biogenesis indices in different groups.Results: Syringic acid significantly attenuated the increase in most of plasma biochemical parameters in diabetic rats. Moreover, syringic acid treatment increased the catalase activity while it reduced the superoxide dismutase activity and hepatic malondialdehyde level in diabetic rats. There was no difference between the glutathione content of the treated and untreated groups. These findings were supported by alleviation of histopathological damages in the syringic acid-treated groups compared to the untreated diabetic group. Syringic acid also significantly up-regulated the hepatic mRNA expression of PGC-1a, NRF-1, and NRF-2 and increased the mtDNA/nDNA ratio in diabetic rats. Conclusions: Syringic acid can be considered as a suitable candidate against hepatic complications since it can reduce oxidative damages in diabetic cases. Furthermore, it has the potential of targeting hepatic mitochondria in diabetes.

Inhibition of liver mitochondrial membrane permeability transition pore opening by quercetin and vitamin E in streptozotocin-induced diabetic rats

Diabetes mellitus is a chronic metabolic disorder characterized by rise in blood glucose levels and generation of free radicals which could induce mitochondrial membrane permeability transition (MMPT) pore opening. This study examined the in vivo action of quercetin and vitamin E on MMPT in the liver of streptozotocin-induced diabetic rats orally pre-treated with 30 mg quercetin/kg body weight (STZQ), 10 mg vitamin E/kg body weight (STZVit.E) and 0.6 mg glibenclamide/kg body weight (STZG). Male albino wistar rats were used in the study and were injected intraperitonially with streptozotocin (STZ) (45 mg/kg body weight) in citrate buffer. The degrees of serum and tissue peroxidation, alanine and aspartate aminotransferase activity were investigated. MMPT pore was assessed as mitochondrial swelling and was monitored spectrophotometrically as changes in absorbance at 540 nm under succinate-energized condition. There was significant increase in serum glucose level, degree of tissue peroxidation, alanine and aspartate aminotransferase activity, cholesterol and triglycerides values in the diabetic control rats following streptozotocin induction. All the treatment had effect on the damage caused by streptozotocin. Quercetin exhibited the highest chemopreventive activity. Quercetin and vitamin E significantly reduced the blood glucose level, degree of tissue peroxidation and alanine and aspartate amino transferase activity. In vivo rat liver MMPT pore was opened in diabetic control rats and significantly inhibited in STZQ, STZV and STZG treated groups by 72.3%, 58.5% and 87.5% respectively. The activity of quercetin and vitamin E were substantiated by histopathological evaluation. Our study suggests that quercetin is an effective therapeutic agent for preventing hepatic tissues from oxidative stress resulting from streptozotocin-induced diabetes by inhibiting apoptotic processes in their target cells.

Insulin glargine affects the expression of Igf-1r, Insr, and Igf-1 genes in colon and liver of diabetic rats.

Objective(s):The mitogenic effect of the analogous insulin glargine is currently under debate since several clinical studies have raised the possibility that insulin glargine treatment has a carcinogenic potential in different tissues. This study aimed to evaluate the Igf-1r, Insr, and Igf-1 gene expression in colon and liver of streptozotocin-induced diabetic rats in response to insulin glargine, neutral protamine Hagedorn (NPH) insulin, and metformin treatments.Materials and Methods:Male Wistar rats were induced during one week with streptozotocin to develop Type 2 Diabetes (T2D) and then randomly distributed into four groups. T2D rats included in the first group received insulin glargine, the second group received NPH insulin, the third group received metformin; finally, untreated T2D rats were included as the control group. All groups were treated for seven days; after the treatment, tissue samples of liver and colon were obtained. Quantitative PCR (qPCR) was performed to analyze the Igf-1r, Insr and Igf-1 gene expression in each tissue sample.Results:The liver tissue showed overexpression of the Insr and Igf-1r genes (P>0.001) in rats treated with insulin glargine in comparison with the control group. Similar results were observed for the Insr gene (P>0.011) in colonic tissue of rats treated with insulin glargine.Conclusion:These observations demonstrate that insulin glargine promote an excess of insulin and IGF-1 receptors in STZ-induced diabetic rats, which could overstimulate the mitogenic signaling pathways.

Proteomic Analysis of Differentially-Expressed Proteins in the Liver of Streptozotocin-Induced Diabetic Rats Treated with Parkia biglobosa Protein Isolate

Protein isolate from Parkia biglobosa seeds is believed to possess excellent anti-diabetic properties. The purpose of this study was to identify differentially expressed proteins in liver of streptozotocin-induced diabetic rats treated with Parkia biglobosa seeds protein isolate (PBPi). In this study, total proteins extracted from rat liver were separated on one-dimensional SDS polyacrylamide gel (1D SDS-PAGE) and stained with Coomassie brilliant blue (CBB) to visualize protein bands. We observed that protein bands in the region of 10–15 kDa were altered by the different treatments; these bands were selected and excised for in-gel digestion and peptide extraction followed by nLC-MS, MALDI-TOF MS, and LIFT MS/MS. A database search with the Mascot algorithm positively identified four differentially expressed proteins. These proteins are known to be responsible for diverse biological functions within various organs and tissues. The present result gives insight and understanding into possible molecular mechanisms by which streptozotocin causes various alterations in proteins found in the liver of diabetic rats and the possible modulatory role of PBPi in the management of streptozotocin-induced diabetes.

Protective effect of aqueous extracts from Canarium odontophyllum Miq. leaf on liver in streptozotocin-induced diabetic rats

The fruit of Canarium odontophyllum Miq. are a traditional delicacy in Borneo for its anti-aging benefit. This study evaluated the protective effect of C. odontophyllum leaf aqueous extract on the damaged liver in streptozotocin-induced diabetic rats. A total of 30 male Spraque-Dawley rats (150-250g) were randomly divided into three groups: control group, diabetic without treatment and diabetic treated with 300 mg/kg aqueous extract once a day for 28 days. The diabetic condition was induced by intravenous injection of 65 mg/kg streptozotocin (STZ). The blood was collected to assess the biochemical changes and the oxidative stress marker whereas the liver section was examined for morphological changes. Result showed that the level of blood aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in STZ-induced rats treated with C. odontophyllum were significantly reduced (p<0.05) compared to STZ group. Oxidative stress test showed lower level of malondealdehid (MDA) and protein carbonyl but significantly (p<0.05) higher activity of GSH, SOD and GPx compared to untreated diabetic group. Abnormal cells were not detected from the histological observation. These findings demonstrated that the aqueous extract of C. odontophyllum has the potential to provide protective effect against liver damage in diabetic rat.

Russelioside B, a pregnane glycoside ameliorates hyperglycemia in streptozotocin induced diabetic rats by regulating key enzymes of glucose metabolism

An alternative strategy to treat diabetes mellitus is the use of various natural agents possessing hypoglycemic effect. Caralluma quadrangula has been used in Saudi traditional medicine in cases of thirst and hunger and for the treatment of diabetes. The present study was designed to evaluate the improving effect of russelioside B, a pregnane glycoside isolated from Caralluma quadrangula on glucose metabolism in the liver of streptozotocin-induced diabetic rats. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Experimental rats were administered russelioside B at a dose of 50 mg/kg body weight once a day for 30 days. The results showed that RB improved the fasting serum glucose level, glycated hemoglobin percent, serum insulin level and lipid profile. A significant improvement was observed upon the administration of russelioside B on the activities of the key enzymes of carbohydrate metabolism (glucokinase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and glycogen phosphorylase) in the liver of diabetic rats. Further, russelioside B administration to diabetic rats reverted gene expression of glucokinase, glucose-6-phosphatase, glycogen synthase and glycogen synthase kinase-3β to near normal levels. In conclusion, russelioside B possess antidiabetic and antihyperlipidemic effect in streptozotocin induced diabetic rats. Hence, administration of russelioside B may represent a potentially useful strategy for the management of diabetes.

Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats.

Background To investigate the protective effects of Quercetin administration associated with chronic moderate exercise (training) on oxidative stress in the liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that performed exercise training were subjected to a swimming training program (1 hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant, Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all animals were sacrificed and liver samples were collected for estimation: some oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG) glutathione ratio. Results Diabetic rats submitted to exercise training showed significantly increased the oxidative stress markers (MDA and PC) and a reduction of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in hepatic tissues. A decrease in the levels of oxidative stress markers associated with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio in the hepatic tissue were observed in Quercetin-treated diabetic trained rats. Conclusions These findings suggest that Quercetin administration in association with chronic moderate exercise exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress in hepatic tissue.

Perfluorononanoic acid disturbed the metabolism of lipid in the liver of streptozotocin-induced diabetic rats

Most studies on the liver toxicity of perfluorinated compounds (PFCs) are focused on healthy individuals, whereas the effects of PFCs on individuals with diabetes mellitus have not been fully characterized. This study aimed to investigate the acute exposure of perfluorononanoic acid (PFNA) on the metabolism of lipid in the liver of streptozotocin-induced diabetic rats. Male diabetic rats were orally dosed by gavage for 7 days with 0, 0.2, 1 and 5 mg/kg/day PFNA. The contents of lipid, the activities of enzyme, the expressions of protein in the liver and the serum parameters were detected. The results indicate that dose-dependent accumulation of triglyceride and total cholesterol occurred in the livers of diabetic rats after PFNA treatment. PFNA increased the activities of lipid synthetase, fatty acid synthease, glucose-6-phosphate dehydrogenase and decreased the activity of lipolytic enzyme, hepatic lipase, in the liver of diabetic rats. The changes of the isocitrate dehydrogenase, malicenzyme and lipoprotein lipase were not obvious. The expressions of protein related to lipid homeostasis, liver X receptor α and apolipoprotein E, were decreased after PFNA administration. Exposure to PFNA also increased the activity of serum alanine aminotransferase in diabetic rats. In conclusion, this study discloses that exposure to PFNA impacts on enzymes and proteins related to liver lipid metabolism and lead to obvious accumulation of lipid in the liver of diabetic rats, which may be responsible for hepatotoxicity of this compound in individuals with diabetes mellitus.

Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats.

Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats. Thirty male Sprague-Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks. GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (P<0.05) levels. It increased liver superoxide dismutase, catalase and glutathione peroxidase activities and albumin level (P<0.05). Administration of GSP significantly ameliorated structural changes induced in liver of diabetic rats. GSP have protective effects against hepatic tissue injury due to antioxidant properties.

Administration of a β-glucan-enriched extract activates beneficial hepatic antioxidant and anti-inflammatory mechanisms in streptozotocin-induced diabetic rats

The beneficial effect of a commercially available β-glucan-enriched extract (BGEE) from cereal grain, against a diabetes-induced hepatic redox imbalance and inflammatory response in streptozotocin-induced diabetic rats was evaluated. Diabetic rats that were treated with BGEE exhibited lower hyperglycaemia and improved biochemical parameters of liver damage. BGEE attenuated hepatic oxidative stress, revealed by a decreased concentration of thiobarbituric acid reactive substances and a restored GSH/GSSG ratio. BGEE also exerted an anti-inflammatory effect on the liver, evidenced by the normalization of the serum concentrations of the “positive” and “negative” acute-phase proteins, α2-macroglobulin and albumin, respectively, as well as by upregulation of anti-inflammatory cytokine IL-10 and IL-4 mRNA expression, and inhibition of RAGE/NF-κB signaling. These findings suggest that BGEE application exerts a beneficial effect in the liver of streptozotocin-induced diabetic rats via its antioxidant and anti-inflammatory activities, and that it therefore possesses an important potential in diabetes management.

Mesobiliverdin IXα Enhances Rat Pancreatic Islet Yield and Function

The aims of this study were to produce mesobiliverdin IXα, an analog of anti-inflammatory biliverdin IXα, and to test its ability to enhance rat pancreatic islet yield for allograft transplantation into diabetic recipients. Mesobiliverdin IXα was synthesized from phycocyanobilin derived from cyanobacteria, and its identity and purity were analyzed by chromatographic and spectroscopic methods. Mesobiliverdin IXα was a substrate for human NADPH biliverdin reductase. Excised Lewis rat pancreata infused with mesobiliverdin IXα and biliverdin IXα-HCl (1–100 μM) yielded islet equivalents as high as 86.7 and 36.5%, respectively, above those from non-treated controls, and the islets showed a high degree of viability based on dithizone staining. When transplanted into livers of streptozotocin-induced diabetic rats, islets from pancreata infused with mesobiliverdin IXα lowered non-fasting blood glucose (BG) levels in 55.6% of the recipients and in 22.2% of control recipients. In intravenous glucose tolerance tests, fasting BG levels of 56 post-operative day recipients with islets from mesobiliverdin IXα infused pancreata were lower than those for controls and showed responses that indicate recovery of insulin-dependent function. In conclusion, mesobiliverdin IXα infusion of pancreata enhanced yields of functional islets capable of reversing insulin dysfunction in diabetic recipients. Since its production is scalable, mesobiliverdin IXα has clinical potential as a protectant of pancreatic islets for allograft transplantation.

Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.