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Concept
Streptozotocin
Summary
Streptozotocin or streptozocin (INN, USP) (STZ) is a naturally occurring alkylating antineoplastic agent 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 hyperglycemia and Alzheimer's in a large dose, as well as type 2 diabetes or type 1 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.
Due to its high toxicity to beta cells, in scientific research, streptozotocin has also been long used for inducing insulitis and diabetes on experimental animals. Streptozotocin has also been used for modeling Alzheimer's disease through memory loss in mice.
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 PARP which is likely more important for diabetes induction than the 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.
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Pancreatic neuroendocrine tumor
Pancreatic neuroendocrine tumours (PanNETs, PETs, or PNETs), often referred to as "islet cell tumours", or "pancreatic endocrine tumours" are neuroendocrine neoplasms that arise from cells of the endocrine (hormonal) and nervous system within the pancreas. PanNETs are a type of neuroendocrine tumor, representing about one-third of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Many PanNETs are benign, while some are malignant. Aggressive PanNET tumors have traditionally been termed "islet cell carcinoma".
Insulinoma
An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a minority metastasize. Insulinomas are one of the functional pancreatic neuroendocrine tumour (PNET) group ("functional" because it increases production of insulin). In the Medical Subject Headings classification, insulinoma is the only subtype of "islet cell adenoma".
Pancreatic islets
The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose. There are about 1 million islets distributed throughout the pancreas of a healthy adult human, each of which measures an average of about 0.