Open Access Articles- Top Results for Streptozotocin
Research & Reviews: Journal of Pharmacology and Toxicological StudiesHypoglycemic Effect of 6-Gingerol, an Active Principle of Ginger in Streptozotocin Induced Diabetic Rats
Pancreatic Disorders & TherapyProtective Effects of Retinoic Acid on Streptozotocin-Induced Type I Diabetes
Research & Reviews: Journal of Botanical SciencesCurrent Researches on Plants Having Antidiabetic Potential: An Overview
Journal of Diabetes & MetabolismFatty-Sucrosed Diet/Minimal Dose of Streptozotocin-Treated Rat: A Novel Model of Gestational Diabetes Mellitus, Metabolic and Inflammatory Insight
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Streptozotocin (Streptozocin, STZ, Zanosar®) is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the Islets of Langerhans and used in medical research to produce an animal model for Type 1 diabetes in a large dose as well as Type 2 diabetes with multiple low doses.
Streptozotocin is approved by the U.S. Food and Drug Administration (FDA) for treating metastatic cancer of the pancreatic islet cells. Since it carries a substantial risk of toxicity and rarely cures the cancer, its use is generally limited to patients whose cancer cannot be removed by surgery. In these patients, streptozotocin can reduce the tumor size and reduce symptoms (especially hypoglycemia due to excessive insulin secretion by insulinomas). A typical dose is 500 mg/m2/day by intravenous injection, for 5 days, repeated every 4-6 weeks.
Streptozotocin is a glucosamine-nitrosourea compound. As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the DNA, though other mechanisms may also contribute. DNA damage induces activation of poly ADP-ribosylation, which is likely more important for diabetes induction than DNA damage itself. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2.
Streptozotocin was originally identified in the late 1950s as an antibiotic. The drug was discovered in a strain of the soil microbe Streptomyces achromogenes by scientists at the drug company Upjohn (now part of Pfizer) in Kalamazoo, Michigan. The soil sample in which the microbe turned up had been taken from Blue Rapids, Kansas, which can therefore be considered the birthplace of streptozotocin. Upjohn filed for patent protection for the drug in August 1958 and U.S. Patent 3,027,300 was granted in March 1962.
In the mid-1960s streptozotocin was found to be selectively toxic to the beta cells of the pancreatic islets, the cells that normally regulate blood glucose levels by producing the hormone insulin. This suggested the drug's use as an animal model of diabetes, and as a medical treatment for cancers of the beta cells. In the 1960s and 1970s the National Cancer Institute investigated streptozotocin's use in cancer chemotherapy. Upjohn filed for FDA approval of streptozotocin as a treatment for pancreatic islet cell cancer in November 1976, and approval was granted in July 1982. The drug was subsequently marketed as Zanosar.
Streptozotocin is now marketed by the generic drug company Sicor (Teva).
- Brentjens R, Saltz L (2001). "Islet cell tumors of the pancreas: the medical oncologist's perspective". Surg Clin North Am 81 (3): 527–42. PMID 11459269. doi:10.1016/S0039-6109(05)70141-9.
- Rossini, A. A.; Like, A. A. A; Chick, W. L.; Appel, M. C.; Cahill Jr, G. F. (1977). "Studies of streptozotocin-induced insulitis and diabetes". Proceedings of the National Academy of Sciences of the United States of America 74 (6): 2485–2489. PMC 432197. PMID 142253. doi:10.1073/pnas.74.6.2485.
- Szkudelski T (2001). "The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas.". Physiol Res 50 (6): 537–46. PMID 11829314.
- Wang Z, Gleichmann H (1998). "GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice". Diabetes 47 (1): 50–6. PMID 9421374. doi:10.2337/diabetes.47.1.50.
- Schnedl WJ, Ferber S, Johnson JH, Newgard CB (1994). "STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells". Diabetes 43 (11): 1326–33. PMID 7926307. doi:10.2337/diabetes.43.11.1326.
- Vavra JJ, Deboer C, Dietz A, Hanka LJ, Sokolski WT (1959). "Streptozotocin, a new antibacterial antibiotic". Antibiot Annu 7: 230–5. PMID 13841501.
- Mansford KR, Opie L (1968). "Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotocin or by alloxan". Lancet 1 (7544): 670–1. PMID 4170654. doi:10.1016/S0140-6736(68)92103-X.
- Rerup CC (1970). "Drugs producing diabetes through damage of the insulin secreting cells". Pharmacol Rev 22 (4): 485–518. PMID 4921840.
- Murray-Lyon IM, Eddleston AL, Williams R, Brown M, Hogbin BM, Bennett A, Edwards JC, Taylor KW (1968). "Treatment of multiple-hormone-producing malignant islet-cell tumour with streptozotocin". Lancet 2 (7574): 895–8. PMID 4176152. doi:10.1016/S0140-6736(68)91058-1.