Studies on the Tissue-Disposition and Fate of [14c]streptozotocin With Special Reference to the Pancreatic Islets

Abstract

The tissue-disposition and fate of [14C]streptozotocin, labelled in the methyl-group of the N-nitrosomethylurea side-chain, have been studied in mice. Whole-body autoradiography, quantified by densitometric measurements, showed that the pancreatic islets had a high capacity to accumulate radioactivity after the injection of [14C]streptozotocin. Microautoradiography of the pancreas showed that centrally located cells were labelled while peripherally located cells contained a low labelling, indicating a selective labelling of the \g=b\-cells. A high radioactivity was present in the liver and the cortex of the kidney at most survival intervals.About 17 % of the radioactivity was exhaled as 14CO2 during 6 h, which shows that the methyl group of the N-nitrosomethylurea side-chain is split off. Radioactivity was shown to be incorporated in the acid-insoluble precipitate of the pancreatic islets, the liver, the kidney, and the exocrine pancreas. This may, to a varying extent, be due both to alkylating reactions and to incorporation of radioactivity in the macromolecules of the tissues via normal metabolic pathways. About 44 % of the radioactivity was excreted as unchanged [14C]streptozotocin in the urine during 24 h, while about 1 % of the radioactivity was found in the faeces. Whole-body autoradiography of [14C]streptozotocin in two Chinese hamsters and one rat also showed a high accumulation of radioactivity in the pancreatic islets in these species.Streptozotocin, an N-nitroso compound produced by Streptomyces achromogenes (Vavra et al. 1959-60), possesses diabetogenic properties by selective destruc¬ tion of the pancreatic /î-cells (Rakieten et al. 1963;Schein et al. 1967; Rerup

Cellular apoptosis and cardiac dysfunction in STZ‐induced diabetic rats attenuated by anthocyanins via activation of IGFI‐R/PI3K/Akt survival signaling

“…Both environmental and genetic factors serve as a risk factor in the pathogenesis of type 1 diabetes mellitus. Streptozotocin (STZ) is a broad spectrum antibiotic that specifically recognizes GLUT2 receptor and induces cytotoxic effects in β cells; thereby STZ specifically targets pancreatic β cell and induces DM in rodents . A single dose of STZ can induce type‐I DM in rodents and such animal models are widely used in studying DM associated cardiovascular complications …”

Pancreatic nitric oxide and oxygen free radicals in the early stages of streptozotocin-induced diabetes mellitus in the rat

“…Streptozotocin (STZ) is an agent widely employed to induce experimental diabetes due to its ability to selectively target and destroy insulin-producing pancreatic islet ß-cells (1). Its diabetogenic action has been ascribed to the enhancement of intracellular methylation reactions (2) and to production of nitric oxide (NO) (3,4) and free radicals (5).…”

Effects of sodium nitroprusside on blood glucose concentration, B‐cell morphology and islet glutamate dehydrogenase activity in mice

“…The structural alterations included mitochondrial damage and translocation of Ca'+-containing precipitates. One reason why these compounds did not induce a permanent diabetes might be that they, in contrast with alloxan (9) and streptozotocin (17), are not accumulated in the B-cells under in vivo conditions.…”