High-fat Diet/low-dose Streptozotocin-induced Type 2 Diabetes In Rats Impacts Osteogenesis And Wnt Signaling In Bone Marrow Stromal Cells
High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes in Rats Impacts Osteogenesis and Wnt Signaling in Bone Marrow Stromal Cells Contributed equally to this work with: Chao Qian, Chenyuan Zhu Affiliation: Department of Prosthodontics, School of Stomatology, Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology. Shanghai, 200011, Peoples Republic of China Contributed equally to this work with: Chao Qian, Chenyuan Zhu Affiliation: Department of Prosthodontics, School of Stomatology, Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology. Shanghai, 200011, Peoples Republic of China Affiliation: Department of Prosthodontics, School of Stomatology, Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology. Shanghai, 200011, Peoples Republic of China * E-mail: [email protected] (FZ); [email protected] (XJ) Affiliation: Department of Prosthodontics, School of Stomatology, Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology. Shanghai, 200011, Peoples Republic of China These authors also contributed equally to this work. * E-mail: [email protected] (FZ); [email protected] (XJ) Affiliation: Department of Prosthodontics, School of Stomatology, Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology. Shanghai, 200011, Peoples Republic of China These authors also contributed equally to this work. Bone regeneration disorders are a significant problem in patients with type 2 diabetes mellitus. Bone marrow stromal cells (BMSCs) are recognized as ideal seed cells for tissue engineerin Continue reading >>
Propolis Effect On Streptozotocin-induced Diabetic Rats
Propolis is one of the hive products that has been used extensively in folk medicine, due to its several biological and pharmacological properties. Besides, propolis-containing products have been intensely marketed by the pharmaceutical industry and health-food stores. This work was carried out in order to investigate whether propolis treatment could revert the metabolic alterations of streptozotocin-induced diabetic rats. Animals were kept in metabolic cages and diabetes was induced by a single dose of streptozotocin (35 mg/kg, IV). After a week, rats with glycemia higher than 230 mg/dL were divided into two groups and treated with ethanolic extract of propolis (10 and 90 mg/kg, PO) for seven days. Glycemia and free fatty acids were determined, as well as food and water intake, body weight and urine volume were registered weekly. Data showed no significant differences in the analyzed variables. Based on these results, one may conclude that propolis had no effects after diabetes establishment, in our conditions assays. Further assays with different concentrations of propolis and periods of administration should be carried out in order to evaluate its therapeutic potential in this disease. Key words: Brazilian propolis, diabetes, glucose, free fatty acids. Propolis is a resinous material collected by bees from buds and plant exudates, which is mixed with products of their salivary glands and wax. The use of propolis dates back to ancient times, and it has been utilized as a medicine in several parts of the world, both for internal or external use. Nowadays, propolis has attracted researchers' interest due to its several therapeutic activities, such as immunomodulatory, antitumor, antimicrobial, anti-inflammatory and antioxidant effects, among others (1). After its admin Continue reading >>
Spontaneous Glucose Intolerance In The Progeny Of Low Dose Streptozotocin-induced Diabetic Mice
, Volume 36, Issue12 , pp 12451251 | Cite as Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice Multiple low doses of streptozotocin (LDS) induce low-incidence diabetes mellitus in Balb/cHan and high-incidence diabetes in CD-1 mice. We studied offspring of diabetic parents in both strains. Group 1 consisted of litters from control mice with no streptozotocin treatment. Group 2 litters had an LDS diabetic mother and a control father, group 3 litters had control mother with LDS diabetic father, and group 4 litters had both, LDS diabetic mother and father. Diabetes was induced by 540 mg streptozotocin per kg on five consecutive days. Progeny of diabetic mothers showed a state of reduced glucose tolerance associated with reduced glucose disappearance during intravenous glucose tolerance test and increased insulin secretion of isolated islets of Langerhans. These metabolic abnormalities predominated in the male litters of both strains of mice. Amniotic insulin was increased in diabetic mothers during pregnancy. No histologic abnormalities were observed in group 2 progeny. Pancreases in male offspring of LDS diabetic CD-1 fathers (group 3) were studied for insulitis. Insulitis was found in 40% of mice with normal glucose tolerance. A single subdiabetogenic dose of streptozotocin (40 mg/kg) induced insulitis in 90% of pancreases accompanied by reduced insulin release of isolated islets. By contrast, male Balb/cHan progeny of diabetic fathers failed to develop insulitis. In conclusion, we found (1) parental LDS diabetes was transmitted more often to male offspring, (2) maternal LDS diabetes was associated with hyperinsulin secretion and glucose intolerance in the offspring and (3) paternal LDS diabetes was accompanied by insulitis a Continue reading >>
Guidelines On Use Of Streptozotocin In Rodents
Guidelines on Use of Streptozotocin in Rodents To describe the appropriate use of streptozotocin for induction of diabetes mellitus (DM) in rats and mice and associated husbandry procedures To describe the appropriate post-injection monitoring of rodents Investigators using STZ to induce diabetes in rodents Streptozotocin (STZ): An antitumor/antibiotic compound isolated from Streptomyces achromogenes with potent toxicity to beta islet cells of the pancreas Carcinogen: An agent capable of causing cancer Teratogen: An agent capable of causing developmental abnormalities Cytotoxic: Possessing ability to exert toxic effects on a cell Depending on the dose and dose frequency, STZ can be used to induce insulin-dependent Type 1 DM or non insulin-dependent Type 2 DM. Known to cause hepatic and renal toxicity in mice and rats. Due to toxic effects and disease progression, some animal mortality can occur. However, steps to reduce mortality must be taken. Is a carcinogen, teratogen, and has been shown to affect fertility in animal studies. Effect on different strains is variable. ULAM recommends starting at the lower end of the dose ranges until performance for a given strain can be established. Increased appetite, defecation, thirst, and urination Appropriate availability of water must be ensured (e.g., if water bottles are being supplied, consider providing two bottles). Cage change frequency may need to be increased to account for increased urination . Recommended doses vary considerably due to strain, age, and weight differences in susceptibility to STZ, as well as variation in the bioactivity of the STZ itself. A general range for use is 42-65 mg/kg administered intraperitoneally (IP). The compound may also be administered intravenously (IV) or by other less common routes. A Continue reading >>
Stz Frequently Asked Questions
Streptozotocin (STZ) is an alkylating agent that affects pancreatic islets, inducing diabetes in mice. The males of various strains are differentially susceptible to developing diabetes: FVB/NJ (001800), BALB/cJ (000651), and A/J (000646) males are resistant; C57BL/6J (000664) males are moderately susceptible; and NOD/ShiLtJ (001976) and CBA/J (000656) males are highly susceptible. NOD-congenic strains like NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG; 005557) and NOD.CB17-Prkdcsci/J (NOD scid; 001303) are also highly susceptible. We have developed a multiple low dose STZ protocol that induces diabetes in C57BL/6J, NSG and NOD scid males. What is the JAX protocol for STZ-induced diabetes? Six- to eight-week old C57BL/6J (000664, B6) or NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (005557,NSG) or NOD.CB17-Prkdcscid/JNOD scid ( 001303, NOD scid) males are individually marked, weighed, and their baseline blood glucose levels determined ((OneTouch Ultra monitor) Mice receive daily IP injections of 50 mg STZ/kg body weight (the most effective dose for B6 males) or 40 mg STZ/kg body weight (for NSG males) for five consecutive days; age-matched controls receive bufferonly injections Because mice metabolize STZ for at least 24 hours post-injection, they are housed in disposable cages with appropriate absorbent bedding and food and water ad libitum At least 24-hours after the final injection, all mice are moved to clean cages, weighed, and their blood glucose levels determined The mice are observed daily until 14-16 days post injection, when they are weighed and their blood glucose levels determined (at this time, pancreatic beta-islet cells are totally absent or severely depleted) Blood glucose level and body weight data for individual mice are shipped with the mice How soon and late after being Continue reading >>
The Characterization Of High-fat Diet And Multiple Low-dose Streptozotocin Induced Type 2 Diabetes Rat Model
The Characterization of High-Fat Diet and Multiple Low-Dose Streptozotocin Induced Type 2 Diabetes Rat Model Department of Pharmacology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, China Received 5 June 2008; Revised 14 October 2008; Accepted 19 November 2008 Copyright 2008 Ming Zhang et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. Based on the previously established method, we developed a better and stable animal model of type 2 diabetes mellitus by high-fat diet combined with multiple low-dose STZ injections. Meanwhile, this new model was used to evaluate the antidiabetic effect of berberine. Method. Wistar male rats fed with regular chow for 4 weeks received vehicle (control groups), rats fed with high-fat diet for 4 weeks received different amounts of STZ once or twice by intraperitoneal injection (diabetic model groups), and diabetic rats were treated with berberine (100 mg/kg, berberine treatment group). Intraperitoneal glucose tolerance test and insulin tolerance test were carried out. Moreover, fasting blood glucose, fasting insulin, total cholesterol, and triglyceride were measured to evaluate the dynamic blood sugar and lipid metabolism. Result. The highest successful rate (100%) was observed in rats treated with a single injection of 45 mg/kg STZ, but the plasma insulin level of this particular group was significantly decreased, and ISI has no difference compared to control group. The successful rate of 30 mg/kg STZ twice injection group was significantly high (85%) and the rats in this group presented a typical characteristic of T2DM as insulin res Continue reading >>
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Hypoglycemic Effect Of Catalpol On High-fat Diet/streptozotocin-induced Diabetic Mice By Increasing Skeletal Muscle Mitochondrial Biogenesis
Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education Jiangsu Center for Pharmacodynamics Research and Evaluation Jiangsu Center for Pharmacodynamics Research and Evaluation Correspondence address. Tel: +86-25-83271043; Fax: + ; E-mail: [email protected] (T.W.)/ [email protected] (L.Z.) Search for other works by this author on: State Key Laboratory of Natural Medicines Correspondence address. Tel: +86-25-83271043; Fax: + ; E-mail: [email protected] (T.W.)/ [email protected] (L.Z.) Search for other works by this author on: Acta Biochimica et Biophysica Sinica, Volume 46, Issue 9, 1 September 2014, Pages 738748, Xia Li, Zhimeng Xu, Zhenzhou Jiang, Lixin Sun, Jinzi Ji, Jingshan Miao, Xueji Zhang, Xiaojie Li, Shan Huang, Tao Wang, Luyong Zhang; Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis, Acta Biochimica et Biophysica Sinica, Volume 46, Issue 9, 1 September 2014, Pages 738748, Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin-induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mitochondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice daily for 4 weeks. Body weight (BW), fast Continue reading >>
Multiple Low Dose Streptozotocin-induced Diabetes In The Rat Causes Acute Upregulation Of Plasma Osteopontin (opn): Protective Role Of Opn In The Islets
Multiple Low Dose Streptozotocin-Induced Diabetes in the Rat Causes Acute Upregulation of Plasma Osteopontin (OPN): Protective Role of OPN in the Islets Osteopontin (OPN) is a secrete Osteopontin (OPN) is a secreted acidic phosphoprotein that binds to a cell surface integrin-binding motif and is involved in many inflammatory and immune-modulating disorders. In a rat diabetes model secondary to multiple injections of low-dose streptozotocin (MLDS) we examined the serum and pancreatic levels of OPN. OPN serum levels were increased 4-fold 24hr after the first dose of streptozotocin and increased 8-fold by day 6. Western blotting of the serum demonstrated an increase of the various soluble molecular weight forms of OPN. Variable patterns of OPN expression were seen in the pancreatic ducts and in islets. After MLDS the intensified OPN expression became more localized towards the periphery of the islets and surrounded the remaining insulin-positive cells. The enhanced OPN reactivity was not associated with accumulation of monocyte/macrophages until day 6. Addition of OPN protein to isolated islets [italic]in vitro[/italic] did not significantly reduce nitric oxide levels. Addition of IL-1[beta] to the islets significantly increased the constitutive expression of both OPN mRNA and OPN protein. Pretreatment of the islets with OPN decreased cytokine-induced nitric oxide production 4-fold, and significantly (P[le] 0.005) reduced induced nitric oxide synthase mRNA and protein levels. OPN prevented IL-1[beta]-mediated inhibition of glucose stimulated insulin secretion in rat islets in a dose-dependent manner. Our data suggest that the acute induction of OPN might represent an endogenous mechanism to protect the islets against cytokine-induced cytotoxicity. ANAND K. KATAKAM, JAGADE Continue reading >>
A New Method For Targeted And Sustained Induction Of Type 2 Diabetes In Rodents
A New Method for Targeted and Sustained Induction of Type 2 Diabetes in Rodents Scientific Reportsvolume7, Articlenumber:14158 (2017) Type 2 diabetes is a chronic metabolic disorder that is becoming a leading cause of morbidity and mortality. The prolonged time-course of human type 2 diabetes makes modelling of the disease difficult and additional animal models and methodologies are needed. The goal of this study was to develop and characterise a new method that allows controlled, targeted and sustained induction of discrete stages of type 2 diabetes in rodents. Using adult, male rats, we employed a three-week high fat-diet regimen and confirmed development of obesity-associated glucose intolerance, a key feature of human type 2 diabetes. Next, we utilised osmotic mini-pumps to infuse streptozotocin (STZ; doses ranging 80200 mg/kg) over the course of 14-days to decrease insulin-producing capacity thus promoting hyperglycemia. Using this new approach, we demonstrate a dose-dependent effect of STZ on circulating glucose and insulin levels as well as glucose tolerance, while retaining a state of obesity. Importantly, we found that insulin secretion in response to a glucose load was present, but reduced in a dose-dependent manner by increasing STZ. In conclusion, we demonstrate a novel method that enables induction of discrete stages of type 2 diabetes in rodents that closely mirrors the different stages of type 2 diabetes in humans. Among the different forms of diabetes, type 2 diabetes accounts for approximately 90% of cases and current estimates indicate that by 2040, approximately 642 million world-wide people will be living with type 2 diabetes 1 , 2 . This is likely to be a conservative estimate given that for every case of diagnosed type 2 diabetes, we know there is Continue reading >>
Springerprotocols: Full Text: Streptozotocin, Type I Diabetes Severity And Bone
Streptozotocin, Type I Diabetes Severity and Bone As many as 50% of adults with type I (T1) diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ)-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2). An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone p Continue reading >>
Early Manifestations In Multiple-low-dose Streptozotocin-induced Diabetes In Mice
Objective:Administration of multiple low doses of streptozotocin (mld-SZ) to mice results in the development of autoimmune diabetes. Hyperglycemia does not develop until a few days after the last injection. In this study, we explored immune-related alterations found in the very early stages of this diabetic syndrome and the capacity of mononuclear spleen cells (MSs) from mld-SZ mice to impair insulin secretion. Methods:Mice injected with mld-SZ were used as an animal model of type 1 diabetes. MSs were isolated from control and mld-SZ mice at days 4, 6, 9, 12, and 16 after the first injection of the diabetogenic drug. MSs were transferred to normal syngeneic recipients or were cocultured with dispersed rat islet cells as an in vitro insulin secretion study. Results:MSs from mld-SZ mice were able to diminish insulin secretion when transferred to normal syngeneic recipients and presented anti--cell immune aggression when cocultured with dispersed rat islet cells as early as day 4 after mld-SZ administration. This capacity persisted throughout the experimental period. As early as 6 days after mld-SZ, islets showed insulitis followed by cell death with progressive severity. Hyperglycemia and diminished insulin secretion from perifused pancreatic islets only appeared at day 9 after mld-SZ. Conclusions:This study suggests that transferred or cocultured MSs from mld-SZ mice exert a functional immune aggression against cells at a very early stage, before donor mice develop impaired insulin secretion and hyperglycemia. From the *Centro de Investigaciones Endocrinolgicas (CEDIE), CONICET, Hospital de Nios Ricardo Gutirrez, Buenos Aires, Argentina; Ctedra de Animales de Laboratorio y Bioterio, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Argentina; Centro N Continue reading >>
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Streptozotocin-induced Experimental Diabetes In Male Wistar Rats.
Gen Physiol Biophys. 1999 Oct;18 Spec No:54-62. Streptozotocin-induced experimental diabetes in male Wistar rats. Institute of Experimental Pharmacology Slovak Academy of Sciences, Bratislava. The aim of the present work was to test the sensitivity of young male Wistar rats, Dobr Voda (Dv:WI) to the diabetogenic effect of streptozotocin (STZ) with regard to their health condition and mortality rates. Eight-week-old rats, weighing from 200 to 230 g, were randomised into five groups of eight animals. Streptozotocin was administered by i.v. injection in doses of 40, 50, 60 and 70 mg/kg body weight. The animals were kept on a standard diet with free access to water for 4 months. The highest STZ dose (70 mg/kg) was lethal to the animals, the doses of 50 and 60 mg/kg induced persistent hyperglycaemia with glucose levels above 20 mM. Body weights of STZ treated rats from all experimental groups were significantly lower than those of control animals. Considerable polyuria was observed in all STZ treated rats. About 40% of the STZ treated animals were found to develop overt cataract between days 90 and 100. At the end of the experiment, significant albuminuria was observed in the experimental groups administered 50 and 60 mg/kg STZ doses. We conclude that young male Wistar rats, Breeding Facility Dobr Voda (Dv:WI), Slovakia, treated by a single i.v. STZ dose of 50 or 60 mg/kg developed a persistent disease state characterised by severe hyperglycaemia with major clinical signs of diabetes mellitus. Continue reading >>
Jci -multiple Low-dose Streptozotocin-induced Diabetes In The Mouse. Evidence For Stimulation Of A Cytotoxic Cellular Immune Response Against An Insulin-producing Beta Cell Line.
Mice were examined for the presence of splenocytes specifically cytotoxic for a rat insulinoma cell line (RIN) during the induction of diabetes by streptozotocin (SZ) in multiple low doses (Multi-Strep). Cytotoxicity was quantitated by the release of 51Cr from damaged cells. A low but statistically significant level of cytolysis (5%) by splenocytes was first detectable on day 8 after the first dose of SZ. The cytotoxicity reached a maximum of approximately 9% on day 10 and slowly decreased thereafter, becoming undetectable 42 d after SZ was first given. The time course of the in vitro cytotoxic response correlated with the degree of insulitis demonstrable in the pancreata of the Multi-Strep mice. The degree of cytotoxicity after Multi-Strep was related to the number of effector splenocytes to which the target RIN cells were exposed and was comparable to that detectable after immunization by intraperitoneal injection of RIN cells in normal mice. The cytotoxicity was specific for insulin-producing cells; syngeneic, allogeneic, and xenogeneic lymphocytes and lymphoblasts, 3T3 cells, and a human keratinocyte cell line were not specifically lysed by the splenocytes of the Multi-Strep mice. This phenomenon was limited to the Multi-Strep mice. Splenocytes from mice made diabetic by a single, high dose of SZ exhibited a very low level of cytotoxicity against the RIN cells. The cytotoxic response was also quantitated in splenocytes from control and Multi-Strep mice (10 d after the first dose of SZ) before and after culture with mitomycin-treated RIN cells in the presence of T cell growth factor (TCGF). The cytotoxicity of the Multi-Strep splenocytes was enhanced more than fivefold after such culture, suggesting the proliferation of an effector cell that could be stimulated and Continue reading >>
Low-dose Streptozotocin-induced Diabetes In The Spontaneously Hypertensive Rat - Sciencedirect
Get rights and content Streptozotocin (STZ, 35 mg/kg body weight) was injected into spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and plasma glucose and triglyceride concentrations measured 10 days later. Neither mean (SEM) plasma glucose (130 3 v 136 3 mg/dL) nor triglyceride (93 6 v 108 7 mg/dL) concentrations increased in WKY rats. In contrast, both plasma glucose (141 3 v 262 36) and triglyceride (121 8 v 196 7 mg/dL) concentrations increased significantly (P < .01) following administration of STZ in SHR. Furthermore, when SHR previously injected with STZ were fed a diet enriched in fructose, they had a further increase (P < .01) in both plasma glucose (343 38 mg/dL) and triglyceride (774 57 mg/dL) concentrations. Plasma triglyceride concentration also increased significantly (P < .05) when STZ-injected WKY rats ingested the fructose-enriched diet, but plasma glucose levels still remained within the normal range (152 5 mg/dL). These results indicate that SHR were more sensitive to the effects of a decrease in pancreatic -cell function (STZ) and an increase in insulin resistance (fructose feeding) than WKY rats. Continue reading >>
