Distribution of Labelled Streptozotocin in Mice: Uptake and Retention in Pancreatic Islets

Tjälve, Hans; Wilander, Erik; Johansson, Eva-Britt

doi:10.1677/joe.0.0690455

Cited by 64 publications

(38 citation statements)

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“…Nitrosoureas are usually lipophilic and tissue uptake through the plasma membrane is rapid; however, as a result of the hexose substitution, streptozotocin is less lipophilic. Streptozotocin is selectively accumulated in pancreatic beta cells via the low-affinity GLUT2 glucose transporter in the plasma membrane [74,75]. Thus, insulin-producing cells that do not express this glucose transporter are resistant to streptozotocin [76][77][78].…”

Section: Beta Cell Selectivity Of Streptozotocinmentioning

confidence: 99%

The mechanisms of alloxan- and streptozotocin-induced diabetes

2007

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Alloxan and streptozotocin are toxic glucose analogues that preferentially accumulate in pancreatic beta cells via the GLUT2 glucose transporter. In the presence of intracellular thiols, especially glutathione, alloxan generates reactive oxygen species (ROS) in a cyclic redox reaction with its reduction product, dialuric acid. Autoxidation of dialuric acid generates superoxide radicals, hydrogen peroxide and, in a final iron-catalysed reaction step, hydroxyl radicals. These hydroxyl radicals are ultimately responsible for the death of the beta cells, which have a particularly low antioxidative defence capacity, and the ensuing state of insulin-dependent 'alloxan diabetes'. As a thiol reagent, alloxan also selectively inhibits glucose-induced insulin secretion through its ability to inhibit the beta cell glucose sensor glucokinase. Following its uptake into the beta cells, streptozotocin is split into its glucose and methylnitrosourea moiety. Owing to its alkylating properties, the latter modifies biological macromolecules, fragments DNA and destroys the beta cells, causing a state of insulin-dependent diabetes. The targeting of mitochondrial DNA, thereby impairing the signalling function of beta cell mitochondrial metabolism, also explains how streptozotocin is able to inhibit glucose-induced insulin secretion.

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Section: Beta Cell Selectivity Of Streptozotocinmentioning

confidence: 99%

The mechanisms of alloxan- and streptozotocin-induced diabetes

2007

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“…Sua estrutura básica é muito semelhante à da glicose, pois ela é facilmente captada pelos transportadores de glicose GLUT-2 10 . Como as células β são mais ativas na captação da glicose, os efeitos citotóxicos da STZ também são mais pronunciados nesse local 11 . A ação tóxica da STZ ocorre por ser um agente alquilante do DNA, fazendo com que a enzima poli (ADP-ribose) polimerase se ative e ocorra depleção de NAD+ celular, levando a redução dos níveis de ATP e, consequentemente, inibição da produção e secreção de insulina 12 .…”

Section: Resultsunclassified

Potencial Diabetogênico da Streptozotocina Em Ratos: Uma Revisão da Literatura

2016

Publ. Biologicas

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reSUmoDevido ao aumento da prevalência do Diabetes Mellitus em diversos países, faz-se necessária a realização de estudos experimentais para o melhor entendimento da sua fisiopatologia. O método químico com utilização prevalente de estreptozotocina para indução de diabetes mellitus em ratos é um dos mais rápidos e de menor custo, sendo esta técnica o foco do presente trabalho. Através de uma minuciosa revisão de literatura, busca-se as descrições atuais do potencial diabetogênico da streptozotocina em ratos. A busca de referências foi realizada nos portais de periódicos MEDLINE e Scielo entre os meses de junho e agosto de 2016. Utilizou-se as seguintes palavras como descritores, em inglês/português: "streptozotocin; diabetes mellitus; rats". A streptozotocina tem sido utilizada em estudos experimentais para induzir o diabetes em modelos animais, porém percebe-se a necessidade de uma padronização em seu uso para que se obtenham resultados mais efetivos durante as pesquisas. Como o resultado final da ação da streptozotocina depende do modelo animal utilizado e também do modo de preparo, via de administração e dose, devemos recordar que todos esses fatores devem ser levados em consideração quando a pesquisa for iniciada, evidenciando a crucial importância de um melhor entendimento de todos os aspectos do mecanismo de ação da streptozotocina na indução do diabetes. O desenvolvimento de mais estudos com o uso de streptozotocina deve ser encorajado, utilizando-se maior amostragem e estirpes mais sensíveis, para que se possa chegar mais próximo de desvendar a completa fisiopatologia do diabetes. Palavras-chave: Streptozotocina. Diabetes Mellitus. Ratos. abStractDue to the increasing prevalence of Diabetes Mellitus disease in several countries, it is necessary to conduct experimental studies to understand all its pathophysiology. One of the cheapest and fastest ways to induce diabetes in murine models is the chemical method using the streptozotocin as the main substance, technique that is the focus of this study. The research was done by a thorough literature review about the current descriptions to the streptozotocin uses and its relationship with the diabetogenic potential. The data basis used were Scielo and MEDLINE jounals web-portals, between June and August 2016, and the keywords (English and Portuguese) were: "streptozotocin; diabetes mellitus; rats". The streptozotocin has widely been using in experimental studies to induce diabetes in animal models. However, it is necessary to have a standardization in its use to achieve the most effective outcome during the research. The results of streptozotocin application depend on the animal model used and also the method of preparation, route of administration and dose. We must consider all of these factors during the experiments, revealing the importance of the knowledge about streptozotocin

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“…The direct and persistence hyperglycemia and hypoinsulinemia in rats after STZ administration is due to the uptake of STZ by pancreatic B-cells via the glucose transporter GLUT2 [40], [41], following which STZ induces alkylation of the DNA of pancreatic beta cell via the nitrosourea moiety of this compound. Moreover, Zafar and Naqvi [42] and Saumya and Basha [43], reported that STZ decompose inside the cell to form carbonium ions that alkylate DNA and decrease cellular nicotinamide adenine nucleotide (NAD) level which may adversely affect beta cells by interrupting respiratory enzyme activity and alteration of their mitochondrial function leading to irreversible cellular necrosis and death of beta cells resulting in permanent hyperglucemia, this changes lead to suppression and disturbance of biosynthesis and insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Mesenchymal Stem cells Infusion Ameliorates Hyperglycemia, Dyslipidemia, Liver and Kidney Functions in Diabetic Rats

2016

IJSR

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Diabetes mellitus is associated with hyperglycemia, lipoprotein abnormalities and various organs dysfunctions. Stem cell therapy offers a great promise for the repair of injured tissues and organs. The aim of this study was to explore the effects of mesenchymal stem cell derived from bone marrow of albino rats on hyperglycemia, hypoinsulinemia, dyslipidemia and liver and kidney dysfunctions in STZ diabetic rats. Rat bone marrow mesenchymal stem cells (BM-MSCs) were isolated, cultured, characterized and finally injected intravenously (2 × 10 6 , via tail vein) into STZ-induced diabetic rats. The other diabetic (STZ) rats received no treatment. The diabetic (STZ) rats showed significant (P<0.05) increase in serum glucose, HbA1c, insulin resistance (IR), total cholesterol, TGs, LDL-C, VLDL-C levels and a significant decrease of serum insulin, HDL-C levels as compared to their corresponding control. Also, higher levels of liver function tests (ALT, AST & ALP) as well as kidney function tests (urea, uric acid and creatinine) were noticed in diabetic rats when compared to control group. Treatment of diabetic rats with MSCs significantly prevented these alterations. These data indicate the efficacy of MSCs transplantation in improving hyperglycemia, dyslipidemia, liver and kidney functions in diabetes mellitus. Further work is required to examine the curative effects on larger animal models and humans.

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Distribution of Labelled Streptozotocin in Mice: Uptake and Retention in Pancreatic Islets

Cited by 64 publications

References 0 publications

The mechanisms of alloxan- and streptozotocin-induced diabetes

The mechanisms of alloxan- and streptozotocin-induced diabetes

Potencial Diabetogênico da Streptozotocina Em Ratos: Uma Revisão da Literatura

Bone Marrow-Derived Mesenchymal Stem cells Infusion Ameliorates Hyperglycemia, Dyslipidemia, Liver and Kidney Functions in Diabetic Rats

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