Streptozotocin Induction Research Articles

Effectiveness and Mechanism of Action of Vanadyl Sulfate in Increasing Pancreatic β Cell Proliferation of DM Mice Due to Streptozotocin Induction

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia as a result of damage to insulin secretion, insulin action, or both. Vanadyl sulfate is one of the form of vanadium which has begun to be used to treat diabetes in humans. In this study, investigation on the effectiveness of vanadyl sulfate in increasing pancreatic β cell proliferation of diabetes mice due to streptozotocin induction. There were 30 healthy mice were subjected to this experimental study. Findings from this experiment proved that administration of vanadyl sulfate at various doses can significantly increase the amount of pancreatic β cell proliferation and eventually reduced blood glucose levels in a meaningless manner. However, those mice that administrated of vanadyl sulfate at a dose of 30 mg/kgBW had a higher amount of Langerhans Islet than those in the vanadyl sulfate group at a dose of 5 mg/kgBW and 100 mg/kgBW. Similar observations were obtained for the Ki-67 expression. The highest Ki-67 expression was obtained at a dose of 30 mg/kgBW but it decreased with a dose of 100 mg/kgBW of vanadyl sulfate.

An untargeted metabolomics approach reveals further insights of Lycium barbarum polysaccharides in high fat diet and streptozotocin-induced diabetic rats

Lycium barbarum polysaccharide (LBP), as one bioactive macromolecular abstracted from goji berry, has shown an abundance of potential function. The present study aimed to evaluate the metabolic effects of LBP on the urine and liver metabolomics on a high-fat diet and streptozotocin-induced diabetic rat model. After 8 weeks of high-fat diet and streptozotocin induction of diabetes, 24 diabetic rats were randomly allocated to the diabetic control (DC) group, LBP low, moderate, and high dosage (LBP-L, LBP-M, LBP-H) groups and 6 non-diabetic rats were established as the non-diabetic control (NDC) group for 30 days' intervention. Metabolomics was performed on liver and urine. LBP positively regulated fasting blood glucose, hemoglobin-A1c, homeostasis model assessment for insulin resistance, liver glycogen and SOD levels significantly, as compared to the DC group. Liver metabolomics showed higher levels of myo-inositol and lower levels of L-malic acid, fumaric acid, D-arabitol, L-allothreonine 1, xylitol, O-phosphorylethanolamine, ribitol, 5-methoxytryptamine 2 and digitoxose 2 in the LBP-H group vs. the DC group, which indicates that LBP may regulate the citrate cycle, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism. Urine metabolomics showed increased levels of creatinine, D-galacturonic acid 2, 2,3-dihydroxybutyric acid and citric acid, and decreased levels of methylmalonic acid, benzoic acid and xylitol between the LBP-H and DC groups. The present study exhibited the effects of LBP on the urine and liver metabolomics in a high-fat diet and streptozotocin-induced rat model, which not only provides a better understanding of the anti-diabetic effects of LBP but also supplies a useful database for further specific mechanism study.

Changes in organ and body weight, serum amylase and antidiabetic effects of tannins from Spondias mombin on streptozotocin-induced diabetic rats

Background: Medicinal plants have been used for centuries in the management of chronic diseases including diabetes.Aim: The purpose of this study is to evaluate the possible antidiabetic effects and changes in serum amylase activities, body weight and organ weight of tannins from Spondias mombin on streptozotocin-induced diabetic rats.Setting: The study was conducted in the department of Biochemistry, University of Benin, Edo state, Nigeria.Methods: A total of 24 albino Wistar rats were divided into four groups (A through D). Group A served as the normal control. Diabetes was induced in rats of groups B, C and D by single-dose intraperitoneal administration of streptozotocin (65 mg/kg body weight) to overnight-fasted rats. Only rats with fasting blood glucose ≥ 250 mg/dL were used for this study. Isolated tannins (100 mg/kg body weight) were administered to rats of group D only. Blood glucose was monitored on Day 0, Day 3, Day 10 and Day 21. After 21 days experimental period blood samples were collected and used for serum amylase activities. Tissues (liver, pancreas, heart and kidney) were excised out and weighed.Results: Tannins-treated rats showed a significant increase in body weight and serum amylase activity when compared with the diabetic control. Also, a significant decrease in blood glucose level was seen in the tannins-treated rats when compared with the diabetic control. A significant decrease in the weight of the pancreas and a significant increase in the weight of the liver were seen in the diabetic control rats when compared with the tannins-treated groups.Conclusion: Tannins of Spondias mombin have an antidiabetic effect and can restore serum amylase and body weight changes resulting from streptozotocin induction.

Hepatoprotective Effect of Gamma-mangostin for Amelioration of Impaired Liver Structure and Function in Streptozotocin-induced Diabetic Mice

The aim of this study was to investigate whether gamma-mangostin could reduce fasting blood glucose, cholesterol, SGOT, SGPT, and also ameliorate damaged hepatocytes in diabetic mice. In this study, we used male BALB/C mice. Mice were divided into two groups: normal control (KN) and streptozotocin-induced diabetic. Streptozotocin (STZ) induction was performed using multiple low doses of 30 mg/kg body weight injected for five consecutive days. The diabetic mice were separated into three subgroups: diabetic control (KD), diabetic mice treated with acarbose (KA), and diabetic mice treated with gamma-mangostin at either 0,5 mg/kg body weight (P1), 1 mg/kg body weight (P2), or 2 mg/kg body weight (P3). Before and after STZ injection, fasting blood glucose and cholesterol level would be observed. Fasting blood glucose and cholesterol level were also measured at the 1st, 7th, and 14th day of gamma-mangostin treatment. Treatment was given for 14 days. On the 15th day, SGOT and SGPT were measured using a Pentra C 200 Reader, while the liver was collected and processed onto the histological slides. Interestingly, we found that gamma-mangostin was able to reduce the fasting blood glucose, cholesterol, SGOT, SGPT, and ameliorate the damaged hepatocytes in significant diabetic mice. Therefore, we concluded that gamma-mangostin is a promising anti-diabetic agent due to its anti-hyperglycemic and antioxidant activities.

Caffeine improves bladder function in streptozotocin-induced diabetic rats.

To examine the protective effects of caffeine in rats with diabetes mellitus (DM) by using urodynamics. Female Sprague-Dawley rats (n = 24) were divided into four groups: control group, DM group, DM + caffeine (5 mg/kg/day), and DM + caffeine (10 mg/kg/day). DM was induced by streptozotocin (STZ). Cystometric studies were conducted on all rats. After 8 weeks of treatment with caffeine, the urodynamic parameters, including bladder capacity, residual urine volume, voiding time, and peak voiding pressure, were measured. DM rats had a higher bladder capacity and post-void residual urine volume (PVR), an increased voiding time and peak voiding pressure, and a markedly lower voiding efficiency than the control group rats. After treatment with caffeine, bladder capacity, post-void residual urine volume, and peak voiding pressure were significant lower than those in the DM group, but voiding efficiency was markedly higher. The results suggested that caffeine (5 or 10 mg/kg/day) may improve the bladder function at 8 weeks after STZ induction. Thus, this may represent a potential strategy to increase voiding efficiency in diabetes.

Antidiabetic potential of purple okra (Abelmoschus esculentus L.) extract in streptozotocin-induced diabetic rats

Okra (Abelmoschus esculentus L.), a tropical vegetable has been reported to have many important biological properties and has been used extensively as a traditional medicine especially for diabetic. In general, the objective of this study was to analyze the potentialof okra extract to body weight and pancreas histopathology in streptozotocin (STZ)-induced diabetic rats and the result will be compared with that of control DM. The experimental design in this study was pre and post test controlled group design. The first step of this study was analyzing the bioactive compound of okra extract. The next step was administiring okra extract to control group and diabetic rats induced by STZ 50 mg/kgBW for 14 days group. Sprague dawley rats were divided into six groups: normal control (N), diabetic control (DM), diabetic treated with green okra extract (GOE) with the dosage of 5 mg/kgBW quercetin and 10 mg/kgBW quercetin, diabetes treated with purple okra extract (POE) with the dosage of 5 mg/kgBW quercetin and 10 mg/kgBW quercetin. Body weight was weighed every three days and pancreas histopathology was measured by immunohistochemistry indirect method. The following results showed that IC50, antioxidant capacity, fenolic, and quercetin contents ofpurple okra extract were higher (316.86 ppm; 417.54 mg/100g; 3.60%; 0.45 mg/g) than green okra extract (326.48 ppm; 341.43 mg/100g; 3.58%; 0.27 mg/g). Administration of GOE I, GOE II, POE I and POE II in diabetic did not give a significant effect to changes in body weight of rats, but effectively could improve repairmen of β cell pancreas destruction due to STZ induction. These results suggest that intervention of green okra extract and purple okra extract based on quercetin compound showed an antidiabetic potency.

Efek Anti Diabetes Spirulina Platensis Terhadap Analisis Kadar, Gambaran Histopatologi, Ekspresi Insulin dan Glucose Transpoter 4 Pada Tikus Putih Wistar yang Diinduksi Streptozopin

Berdasarkan Riset Kesehatan Dasar, di Yogyakarta angka kejadian diabetes melitus berdasarkan diagnosis dokter didapat sebanyak 2,6% dan gejala akan meningkat sesuai bertambahnya umur, namun akan turun mulai umur >65 tahun. Pada pengobatan diabetes melitus ini terdapat beberapa pengobatan dengan obat sintetik dan bahan alam untuk bahan alam salah satunya yaitu Spirulina platensis. Spirulina platensis adalah salah satu mikroalga yang di dalamnya mengandung spektrum alami dari campuran karoten dan pigmen xantofil, dan dengan fikosianin memiliki aktivitas antioksidan, serta Spirulina platensis dapat menunjukan penurunan pada gula darah.
 Jenis penelitian yang dilakukan merupakan penelitian eksperimental. Spirulina platensis dibuat suspensi dengan beberapa macam dosis 36 mg, 72 mg, dan 144 mg. Tikus dibagi 6 kelompok, 5 kelompok diinduksi streptozotosin dengan dosis 45 mg/kgBB hingga tikus mengalami DM ditandai dengan hasil KGD yang tinggi, kemudian di beri suspensi spirulina, di ukur kadar gula pada hari ke 0-28. Setelah itu tikus di ambil darah kemudian dianalisis pengaruh Spirulina platensis terhadap kadar kreatinin dan ureum dalam darah. Hasil dianalisis menggunakan SPSS metode ANOVA dan Post Hoc Test dengan taraf kepercayaan 95%.
 Hasil dari analisis kadar pada berbagai kelompok menunjukan bahwa pada induksi streptozotocin yang diberi perlakuan spirulina plantesis berbagai dosis terdapat perbaikan pada tiap analisis kadar yang didapat, dan juga pada dosis STZ+SP 36 pada tiap analisis dapat memperbaiki kadar analisis. Sedangkan pada hasil histopatologi serta ekspresi insulin pada pankreas dan histologi serta ekspresi glucose transporter 4 serta histopatologi pada ginjal dan hati menunjukan perubahan yang baik pada berbagai kelompok dosis perlakuan terutama pada kelompok STZ+SP 36. Sehingga pada dosis STZ+SP 36 yang menunjukan perubahan yang baik pada penelitian ini.

Tangeretin inhibits streptozotocin-induced cell apoptosis via regulating NF-κB pathway in INS-1 cells.

Oxidative stress is considered to play an important role in inducing the pancreatic β-cells apoptosis and promoting the development of diabetes mellitus. Tangeretin is a plant-derived flavonoid that retains antidiabetic effects. However, the role of tangeretin in streptozotocin (STZ)-induced β-cell apoptosis remains unclear. In this study, we aimed to examine the effects of tangeretin on STZ-induced cell apoptosis and the underlying mechanisms implicated in vitro. Our results showed that tangeretin improved the cell viability in STZ-induced INS-1 cells. Tangeretin reduced the increase of apoptosis ratio and revered the altered expressions of Bax and Bcl-2 caused by STZ induction. Furthermore, the impairment of insulin secretion ability as well as a reduction in messenger RNA levels of insulin 1 and 2 was significantly attenuated by tangeretin in STZ-induced INS-1 cells. Moreover, tangeretin resulted in a significant decrease in reactive oxygen species content, accompanied by an evident increase in the activities of superoxide dismutase, catalase, and glutathione peroxidase. Mechanistic studies further revealed that tangeretin inhibited the NF-κB pathway in STZ-induced INS-1 cells. These data indicated that tangeretin improved the cell apoptosis induced by STZ in INS-1 cells, which might be partly due to its antioxidant potential. Furthermore, NF-κB was found to be involved in the protective effect of tangeretin. Collectively, the results indicated that tangeretin could be used as a therapeutic approach for diabetes mellitus treatment.

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.

Oyster mushroom functions as an anti-hyperglycaemic through phosphorylation of AMPK and increased expression of GLUT4 in type 2 diabetic model rats.

ObjectivesTraditionally, mushrooms have been used to reduce hyperglycaemia. However, the mechanism underlying this effect has not yet been explored. AMP-activated protein kinase (AMPK) is known to reduce hyperglycaemia through an insulin-independent pathway. This study aimed to observe the effect of oyster mushroom powder (OMP) on phosphorylation of AMPK (p-AMPK) and expression of GLUT4 mRNA in diabetic model rats.MethodsLong-Evans rats were used to develop type 2 diabetic model rats through intraperitoneal induction of streptozotocin (STZ). OMP was supplemented at 5% with the usual feed of rats for 8 consecutive weeks. Then, the rats were sacrificed. RNA was extracted by the TRIzol reagent, and proteins were extracted from different tissues with RIPA lysis buffer. Expression of GLUT4 mRNA was measured through cDNA-PCR techniques, and p-AMPK was detected using western blotting. The band intensities of the PCR products and proteins were measured using Image J software.ResultsSupplementation of OMP for 8 weeks resulted in a reduction of the serum glucose level in STZ-induced, type 2 diabetic model rats. The levels of p-AMPK, as a ratio relative to β-actin, increased in the muscle and adipose tissues of mushroom-treated type 2 diabetic model rats, compared to those in control diabetic model rats. Expression of GLUT4, as a ratio relative to GAPDH, increased significantly in both the muscle and adipose tissues of mushroom-treated diabetic rats.ConclusionOyster mushroom may decrease hyperglycaemia through increased p-AMPK and also expression of GLUT4 in the muscle and adipose tissues.

Functionality of cow milk naturally enriched with polyunsaturated fatty acids and polyphenols in diets for diabetic rats.

The increasing incidence of diabetes mellitus is becoming a serious threat to human health in various parts of the world. Studies with dairy products have shown a potential beneficial effect against diabetes. This experiment evaluated the supplementation of milk naturally enriched with polyunsaturated fatty acids (PUFA) and polyphenols in rats with streptozotocin-induced diabetes. Forty male 28-day-old Wistar rats were distributed in four experimental treatments of diabetic animals (streptozotocin induction) and a normal group (non-induced). Experimental treatments were: control (water), whole common milk (COM-M), milk enriched with PUFA (PUFA-M), milk enriched with PUFA and polyphenols (PUFA/P-M) through a special diet offered to dairy cows. Milk supplementation at a dose 5 mL/kg body weight was performed for 77 days, 42 days before and 35 days after diabetes induction. The COM-M supplementation increased brown fat deposits, reduced post-induction glucose levels, reduced blood fructosamine levels, and improved glucose tolerance. Milk enriched with PUFA reduced final fasting glucose, LDL levels, and improved blood antioxidant capacity. Milk enriched with PUFA and polyphenols promoted an increase in gastrocnemius muscle mass, and a reduction in mesenteric fat and LDL levels. Milk intake, with an emphasis on milk enriched with PUFA and polyphenols, attenuated the metabolic disorders of streptozotocin-induced diabetes in rats.

Effects of hyperglycemia on remodeling of acute myocardial infarction in rats

Acute myocardial infarction (MI) remodeling consequences for cardiac function were investigated in diabetes (hyperglycemia) induced by streptozotocin (STZ) in rats. The measurements were performed after 15 days of STZ induction (50 mg/kg iv) and/or 48hs of MI. The following parameters were evaluated: levels of FFA, TG (in plasma and the left ventricle–LV) and glycogen in the LV, the cardiac remodeling, the autonomic nervous system activity, and the oxidative stress in the LV. The Wistar rats (n=8 per group) were divided into 4 groups: control (C); control infarcted (CI); diabetic (D); diabetic infarcted (DI). After 15 days of STZ, the MI was induced by left coronary artery occlusion (□ 25% MI area between the CI and DI groups). The CI group had increased: end‐posterior wall thickness (LVPW), interventricular septum thickness the relative wall thickness and reduced LV cavity, as consequence of cardiac remodeling and increased LV mass. The D group had reduced LVPW (0.11 ± 0.001 cm) as compared with the C (0.13 ± 0.003 cm). DI group had increased LVPW (0.14 ± 0.005 cm). The systolic function was not different between groups. However, the D and CI group exhibited increased isovolumetric relaxation time (IVRT ms): D: 34 ± 1; CI: 30 ± 2.4 vs C: 23 ± 0.7 and The E‐wave desaceleration (ms) was increased in D: 50 ± 0.9 vs C: 40 ± 0.6, having diastolic dysfunction in diabetic rats but there was no impairment in MI (DI: 35 ± 2.3). The variance of heart rate (HRV m2) was reduced by diabetes (D: 18 ± 2.5; DI: 25 ± 3) vs the C group (81 ± 3), as well as the low (LF) and high (HF) frequency bands (sympathetic and vagal components). The MI increased in non‐diabetic rats the HRV (CI: 99 ± 14) and the LF (m2) (CI: 1.8 ± 0.5 vs D: 0.6 ± 0.1; DI: 1 ± 0.2). The variance of blood pressure (mmHg) was reduced by diabetes (D: 8.6 ± 0.7; DI: 5.3 ± 0.6) as compared to C (24 ± 3) and CI (18 ± 3) and the LF were increased only in the CI group (2.7 ± 0.17) vs DI group (1 ± 0.2). The MI increased in non‐diabetic rats the lipid peroxidation (1156 ± 125) vs C: 645 ± 111; D: 945 ± 117; DI: 894 ± 112) and both the MI groups increased the anion superoxide, however, only DI had increased antioxidant enzyme activities (catalase, glutathione peroxidase, superoxide dismutase) improving the redox balance after MI. DI group had reduced TG (1.4 ± 0.19) and glycogen (43 ± 7) content in the LV that was increased before the MI (D: 5.4 ± 0.9 vs C: 1.1 ± 0.2; D: 316 ± 79 vs C: 20 ± 5, respectively mg/g of LV). Therefore, the hyperglycemia previous to ischemia promoted a more efficient metabolic response on remodeling and cardiac function with improved oxidative balance.Support or Funding InformationFAPESP, CNPq, and CAPES supported this research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Leea macrophylla Roxb. leaf extract potentially helps normalize islet of β-cells damaged in STZ-induced albino rats.

This research aims to investigate the protective effects Leea macrophylla Roxb polyphenols on streptozotocin‐induced diabetic rats. Polyphenolic assays were undertaken through established methods. To conduct animal intervention study, forty Wistar albino male rats (average body weight 188.42 ± 7.13 g) of different groups were diabetized by streptozotocin (60 mg/kg) only in the animals of diabetic control (DC) and L. macrophylla extract (LM) groups. At the end of 4 weeks of intervention, serum was analyzed for insulin, liver and cardiac enzymes, lipid profiles, uric acid, and creatinine using ELISA method. In vitro α‐amylase inhibition of LM was evaluated and compared with reference drug acarbose. Pancreatic tissues were undertaken for histopathological screening. Food and fluid intake, weekly blood glucose level, liver glycogen, aspartate transaminase (AST), creatinine kinase (CK‐MB), cholesterol, and lactate dehydrogenase (LDH) were significantly decreased, whereas oral glucose tolerance (OGTT) ability, serum insulin concentration, and pancreatic islets morphology were significantly improved in the LM300 treatment group compared to the DC group. Alpha‐amylase inhibition was not found to be very promising for guiding the α‐amylase inhibition pathway. Results suggest that L. macrophylla can exert a potential effort to restore pancreatic β‐cell damaged by streptozotocin induction.

Hypoglycemic effect of ethyl acetate fraction of methanol extract from Campylandra aurantiaca rhizome on high-fat diet and low-dose streptozotocin-induced diabetic rats

Background: Campylandra aurantiaca (Asparagaceae), commonly known as Nakima in Sikkimese Tibetan, is a plant grown in South-Central China and Northeast India. Objective: To evaluate the hypoglycemic activity of ethyl acetate fraction of methanol extract from C. aurantiaca rhizome (EFCA) in high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced diabetic Wistar rats. Materials and Methods: In rats fed with HFD for 4 weeks, hyperglycemia was induced by single intraperitoneal injection of STZ (35 mg/kg body weight). Seven days after STZ induction, the hyperglycemic rats were treated with EFCA orally at the doses of 100 and 200 mg/kg b.w. daily for 28 days. Glibenclamide (0.5 mg/kg, orally) was used as reference drug. The fasting blood glucose levels were measured on every 7th day during the 28 days of treatment. Serum and hepatorenal biochemical parameters were estimated. Histological study of the pancreas was also performed. Results: EFCA at the doses of 100 and 200 mg/kg orally significantly (P Abbreviations used: IDDM: Insulin-dependent diabetes mellitus, T2DM: Type 2 diabetes mellitus, NIDDM: Noninsulin-dependent diabetes mellitus, T1DM: Type 1 diabetes mellitus, IDF: International Diabetes Federation, STZ: Streptozotocin, EFCA: Ethyl acetate fraction of methanol extract from Campylandra aurantiaca rhizome, OGTT: Oral glucose tolerance test, HFD: High-fat diet, FBG: Fasting blood glucose, HDL: High-density lipoprotein cholesterol, HbA1c: Glycosylated hemoglobin, AST: Aspartate transaminase, ALT: Alanine transaminase, ALP: Alkaline phosphatase, LPO: Lipid peroxidation, GSH: Reduced glutathione, SOD: Superoxide dismutase, CAT: Catalase, SEM: Standard error of mean, ANOVA: Analysis of variance, HPLC: High-performance liquid chromatography.

Effect of liver histopathology on islet cell engraftment in the model mimicking autologous islet cell transplantation

ABSTRACTBackground: The inflammatory milieu in the liver as determined by histopathology is different in individual patients undergoing autologous islet cell transplantation. We hypothesized that inflammation related to fatty-liver adversely impacts islet survival. To test this hypothesis, we used a mouse model of fatty-liver to determine the outcome of syngeneic islet transplantation after chemical pancreatectomy. Methods: Mice (C57BL/6) were fed a high-fat-diet from 6 weeks of age until attaining a weight of ≥28 grams (6–8 weeks) to produce a fatty liver (histologically > 30% fat);steatosis was confirmed with lipidomic profile of liver tissue. Islets were infused via the intra-portal route in fatty-liver and control mice after streptozotocin induction of diabetes. Outcomes were assessed by the rate of euglycemia, liver histopathology, evaluation of liver inflammation by measuring tissue cytokines IL-1β and TNF-α by RT-PCR and CD31 expression by immunohistochemistry. Results: The difference in the euglycemic fraction between the normal liver group (90%, 9/10) and the fatty-liver group (37.5%, 3/8) was statistically significant at the 18th day post- transplant and was maintained to the end of the study (day 28) (p = 0.019, X2 = 5.51). Levels of TNF–α and IL-1β were elevated in fatty-liver mice (p = 0.042, p = 0.037). Compared to controls cytokine levels were elevated after islet cell transplantation and in transplanted fatty-liver mice as compared to either fatty- or islet transplant group alone (p = NS). A difference in the histochemical pattern of CD31 could not be determined. Conclusion: Fatty-liver creates an inflammatory state which adversely affects the outcome of autologous islet cell transplantation.

ANTI-HYPERGLYCEMIC ACTIVITY OF CITRUS LIMON LEAVES IN STREPTOZOTOCIN INDUCED DIABETIC RATS

Citrus limon leaves is a traditional herbal medicine which is used as a munching dietary supplement for the management of diabetes in parts of Kerala. However there is no evidence supporting the claim. The objective of the present study was to evaluate the anti-diabetic effect of Citrus limon leaves extract against streptozotocin (STZ)-induced diabetic rats. Aqueous extract of Citrus limon leaf with the doses of 50 mg/kg and 100 mg/kg were orally administered once a day for 28 days from 3rd day after STZ induction and the results were compared to those for glibenclamide. A decrease in body weight and plasma insulin levels and an increase in blood glucose levels were observed in STZ induced diabetic rats. However, these diabetic changes were significantly and dose dependently inhibited by treatment with Citrus limon leaves extract. This study focus the efficacy of this extract for the management of experimental diabetes in rat model which may shed some light on the scientific basis of ancient herbal therapy.

Ameliorative Effect of Mesenchymal Stromal Cells on Diabetic Nephropathy in Male Rats

Both types of diabetes mellitus (DM) are recognized by the destruction of pancreas or deficient function of Islets’ cells causing several complications. Diabetes mainly affect the kidney leading to diabetic nephropathy (DN) in the late renal stage, which caused higher mortality in diabetic patients. Since diabetic disease appearance, nephropathy may be observed in patients with type 1 or 2 diabetes. Recently, cell culture can be used in the regenerative medicine as a new method for treating diabetes and DN. Therefore, the aim of the current study was to prove the beneficial effect of mesenchymal stromal cells (MSCs) transplantation on DN during the early stage. Male rats were randomized in 3 groups (each 20 rats): the 1st group was normal rats, while the 2 nd was streptozotocin (STZ) diabetic rats and the 3 rd was diabetic rats treated with a single intravenous dose of bone marrow mesenchymal stromal cells (BM-MSCs) after 3 days from STZ induction. Results indicated that STZ induced DN represented by weight loss, hyperglycemia, hypoinsulineamia, decreased glycated hemoglobin, leukocytosis and impairment of kidney function and oxidative stress in kidney tissue. After BM-MSCs treatment, blood glucose level was improved, renal function was retained, body weight loss was decreased, insulin level and HBA1C percent were ameliorated with improved oxidative stress in kidney tissue. BM-MSCs have the capacity to regenerate and differentiate into insulin- producing cells improving DM and DN.

Permanent magnetic field, direct electric field, and infrared to reduce blood glucose level and hepatic function in mus musculus with diabetic mellitus

Blood contains several electrolytes with positive (cation) and negative (anion) ion load. Both electrolytes deliver impulse synergistically adjusting body needs. Those electrolytes give specific effect to external disturbance such as electric, magnetic, even infrared field. A study has been conducted to reduce blood glucose level and liver function, in type 2 Diabetes Mellitus patients, using Biophysics concept which uses combination therapy of permanent magnetic field, electric field, and infrared. This study used 48 healthy mice (mus musculus), male, age 3-4 weeks, with approximately 25-30 g in weight. Mice was fed with lard as high fat diet orally, before Streptozotocin (STZ) induction become diabetic mice. Therapy was conducted by putting mice in a chamber that emits the combination of permanent magnetic field, electric field, and infrared, every day for 1 hour for 28 days. There were 4 combinations of therapy/treatment, namely: (1) permanent magnetic field, direct electric field, and infrared; (2) permanent magnetic field, direct electric field, without infrared; (3) permanent magnetic field, alternating electric field, and infrared; and (4) permanent magnetic field, alternating electric field, without infrared. The results of therapy show that every combination is able to reduce blood glucose level, AST, and ALT. However, the best result is by using combination of permanent magnetic field, direct electric field, and infrared.

NEUROPROTECTIVE POTENTIAL OF AZADIRACHTA INDICA LEAVES IN DIABETIC RATS

Objective: Azadirachta indica is a treasure of multiple pharmacological properties and presently leaves of this plant have been explored to evaluate the neuroprotective potential in diabetic rats.Methods: Male Sprague-Dawley rats were injected with single intra peritoneal dose of streptozotocin (60mg/ Kg body weight (BW.) to develop animal model of diabetes. Post twenty one days of streptozotocin induction, animals were treated with aqueous Azadirachta indica Leaf Extract (ALE, 600mg/Kg BW.) for seven consecutive days. Followed this, all animals were evaluated for the levels of blood glucose, lipid peroxidation (LPO), C Reactive Proteins (CRP), pro oxidant biomarkers and histological changes.Results: Streptozotocin treated rats exhibited elevated levels of blood glucose, LPO, CRP and altered pro oxidant biomarkers in comparison to control rats. Additionally, histological alterations/damage was evidenced as fragmentation, vacuolization, inflammation etc. However, ALE treatment to these rats significantly decreased blood glucose levels, LPO, CRP levels and restored pro-oxidants status. Light microscopic and ultra microscopic analysis also indicated less damage, tissue architectural changes in comparison to untreated diabetic rats. Further decrease in hyperalgesia and inflammation levels; along with protective and restorative changes following ALE treatment suggested the neuroprotective potential of Azadirachta indica leaves in diabetic rats.Conclusion: The oral administration of ALE to streptozotocin induced diabetic animals resulted in neuro-protection against degenerative oxidative stress associated with metabolic and histopathological damage in the brain.Key words: Azadirachta indica, Antioxidants, Hyperalgesia, Neuroprotection

Hyperglycemia caused reduction of cortical bone thickness in streptozotocin-induced diabetic rat

Background: Diabetes is a chronic metabolic disease characterized by hypergyclemia due to insulin deficiency (type 1 diabetes) or insulin insensitivity/resistance (type 2 diabetes). The significant metabolic changes that occur in diabetes also affect the skeleton and cause bone loss and/or altered bone matrix and strength, thereby increasing the risk of fracture. Hyperglycemia can alter cellular metabolic processes through the formation of advanced glycation end products (AGEs), which caused dysregulation of various cytokines as the underlying mechanism in the decrease of bone density. This study aimed to see the bone loss caused by hyperglycemia in rats, using cortical bone thickness as a parameter. Methods: This study was an analytical experimental study, which was conducted in a laboratory. The sample of this study was Wistar rat (Rattus norvegicus). Diabetes in the rats were induced using streptozotocin. The diabetic rats were then sacrificed 11 days later, and the left femur bone was obtanied. The bone was decalcified for 1 week, then prepared for histological slides. Cortical bone thickness was measured microscopically using Optilab Image Raster software at 10 different axis points, and then averaged. Results: The mean of cortical bone thickness were 32.43 ± 2.65 μm in the control (non diabetic) rats, and 26.64 ± 2.89 μm in streptozotocin-induced diabetic rats (p < 0.001). The diabetic rats had lower mean of cortical bone thickness than control by 5.79 μm. Conclusion: Cortical bone thickness in the diabetic rats were lower by 18% compared to control 11 days after induction of streptozotocin.