Mechanisms of Toxic Effect of Streptozotocin on β-Cells in the Islets of Langerhans

Писарев, В. Б.; Снигур, Г Л; Spasov, A. A.; Samokhina, M. P.; Bulanov, A. E.

doi:10.1007/s10517-010-0856-9

Cited by 12 publications

(8 citation statements)

References 9 publications

(7 reference statements)

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“…ЭСД вызывали путем однократного внутрибрю-шинного введения стрептозотоцина (65 мг/кг, «Sigma-Aldrich», США) через 15 мин после введения никотинамида (230 мг/кг, «Sigma-Aldrich», США) [10][11][12]. В эксперимент включали животных с уров-нем глюкозы в крови 8-14 ммоль/л; гликемию из-меряли после 6-часового голодания на 3-и сутки по-сле введения стрептозотоцина (глюкометр Контур ТС).…”

Section: материал и методыunclassified

“…Значимо уменьшилась и относи-тельная площадь инсулин-позитивного материала β-эндокриноцитов (на 43,8%; p<0,001). Сходные ре-зультаты получены и другими авторами на моделях стрептозотоцин-и аллоксаниндуцированного ЭСД [10,11,14].…”

Section: результатыunclassified

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Influence of novel GPR119 receptor agonist on plasma glucose and insulin level, as well as structural changes of pancreas islets in rats with experimental type 2 diabetes

Tyurenkov

Николаевич²,

Куркин

et al. 2016

Probl Endokrinol (Mosk)

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Background. GPR119 receptor is a promising target for novel antidiabetic drugs development because of its agonists in addition to hypoglycemic effects have cytoprotective effect on beta cells.Aim — to assess the effect of the novel GPR119 receptor agonist and sitagliptin on carbohydrate metabolism and morphological structure of the pancreas in animals with experimental type 2 diabetes.Material and methods. The study was performed in Wistar rats with streptozotocin-nicotinamide-induced diabetes. Serum insulin was determined by ELISA (Rat Insulin, (INS) ELISA Kit, 96 CSB). Immunohistochemical studies were performed using mouse monoclonal antibodies to insulin (clone 1G4, GeneTex) with determination of the absolute and relative area of immunopositive material (beta-cells) of the pancreatic islets.Results. 28-day treatment of animals with diabetes by GPR119 receptor agonist — ZB-16 (dipiaron) (1 mg/kg, per os, daily) and an inhibitor of the DPP-4 (sitagliptin) led to a reduction of fasting hyperglycemia and improve its glucose tolerance and enhance basal and stimulated insulin secretion relative to the control without treatment. Morphometric assessment of islets revealed that animals treated with the ZB-16 and sitagliptin have significantly higher absolute and relative islets area, as well as the perimeter of the insulin-positive material compared to islets of rats without treatment.Conclusion. Course administration of GPR119 receptor agonist to animals with streptozotocin-nicotinamide-induced diabetes has a pronounced antidiabetic effect consists in reducing fasting plasma glucose, improve glucose utilization, increase basal and stimulated insulin secretion, as well as increasing the area of the insulin-positive material in islets. Antidiabetic action of novel GPR119 receptor agonist, was comparable to that of sitagliptin.

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Section: материал и методыunclassified

Section: результатыunclassified

Influence of novel GPR119 receptor agonist on plasma glucose and insulin level, as well as structural changes of pancreas islets in rats with experimental type 2 diabetes

Tyurenkov

Николаевич²,

Куркин

et al. 2016

Probl Endokrinol (Mosk)

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“…Furthermore, streptozotocin liberates toxic amounts of nitric oxide that inhibits aconitase activity and participates in DNA damage. As a result of the streptozotocin action, beta cells undergo the destruction by necrosis [30]. In this study, scintigraphic imaging of the streptozotocin-treated rat showed no uptake of 99m Tc-DTPA-GLP in the pancreas compared to baseline studies.…”

Section: Discussionmentioning

confidence: 51%

Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with 99mTc-DTPA-glipizide

Kohanim

Kong

et al. 2012

Ann Nucl Med

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Objective This study was aimed to assess pancreas beta cell activity using 99mTc-diethyleneaminepentaacetic acid-glipizide (DTPA-GLP), a sulfonylurea receptor agent. The effect of DTPA-GLP on the blood glucose level in rats was also evaluated. Methods DTPA dianhydride was conjugated with GLP in the presence of sodium amide, yielding 60%. Biodistribution and planar images were obtained at 30–120 min after injection of 99mTc-DTPA-GLP (1 mg/rat, 0.74 and 11.1 MBq per rat, respectively) in normal female Fischer 344 rats. The control group was given 99mTc-DTPA. To demonstrate pancreas beta cell uptake of 99mTc-DTPA-GLP via a receptor-mediated process, a group of rats was pretreated with streptozotocin (a beta cell toxin, 55 mg/kg, i.v.) and the images were acquired at immediately—65 min on day 5 post-treatment. The effect on the glucose levels after a single administration (ip) of DTPA-GLP was compared to glipizide (GLP) for up to 6 h. Results The structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was >96%. 99mTc-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas 99mTc-DTPA showed decreased ratios at various time points. Pancreas could be visualized with 99mTc-DTPA-GLP in normal rat, however, 99mTc-DTPA has poor uptake suggesting the specificity of 99mTc-DTPA-GLP. Pancreas beta cell uptake could be blocked by pre-treatment with streptozotocin. DTPA-GLP showed an equal or better response in lowering the glucose levels compared to the existing GLP drug. Conclusions It is feasible to use 99mTc-DTPA-GLP to assess pancreas beta cell receptor recognition. 99mTc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors.

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“…[37] All groups demonstrated marked hyperglycemia prior to the experiment. [37] All groups demonstrated marked hyperglycemia prior to the experiment.…”

Section: -Acylbenzofuran Derivativesmentioning

confidence: 95%

Synthesis and biological evaluation of 2‐acylbenzofuranes as novel α‐glucosidase inhibitors with hypoglycemic activity

et al. 2017

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A series of benzofuran derivatives was synthesized as analogues of known natural α-glucosidase inhibitors. Their activity was evaluated in enzymatic assay and in rat model of diabetes mellitus. Newly identified inhibitors demonstrate significant potency with IC values ranging from 6.50 to 722.2 μm, as well as hypoglycemic activity exceeding the reference drug acarbose. Docking simulations provided insight into structure-activity relationships to direct further development of these novel hypoglycemic agents.

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Mechanisms of Toxic Effect of Streptozotocin on β-Cells in the Islets of Langerhans

Cited by 12 publications

References 9 publications

Influence of novel GPR119 receptor agonist on plasma glucose and insulin level, as well as structural changes of pancreas islets in rats with experimental type 2 diabetes

Influence of novel GPR119 receptor agonist on plasma glucose and insulin level, as well as structural changes of pancreas islets in rats with experimental type 2 diabetes

Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with 99mTc-DTPA-glipizide

Synthesis and biological evaluation of 2‐acylbenzofuranes as novel α‐glucosidase inhibitors with hypoglycemic activity

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