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J Clin Invest. Nov 1969; 48(11): 2129–2139.
PMCID: PMC297467

Diabetogenic action of streptozotocin: relationship of dose to metabolic response

Abstract

The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections.

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Selected References

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  • Schein PS, Bates RW. Plasma glucose levels in normal and adrenalectomized mice treated with streptozotocin and nicotinamide. Diabetes. 1968 Dec;17(12):760–765. [PubMed]
  • Dulin WE, Wyse BM. Studies on the ability of compounds to block the diabetogenic activity of streptozotocin. Diabetes. 1969 Jul;18(7):459–466. [PubMed]
  • Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE. Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med. 1967 Oct;126(1):201–205. [PubMed]
  • RAKIETEN N, RAKIETEN ML, NADKARNI MV. Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep. 1963 May;29:91–98. [PubMed]
  • Evans JS, Gerritsen GC, Mann KM, Owen SP. Antitumor and hyperglycemic activity of streptozotocin (NSC-37917) and its cofactor, U-15,774. Cancer Chemother Rep. 1965 Oct;48:1–6. [PubMed]
  • Arison RN, Ciaccio EI, Glitzer MS, Cassaro JA, Pruss MP. Light and electron microscopy of lesions in rats rendered diabetic with streptozotocin. Diabetes. 1967 Jan;16(1):51–56. [PubMed]
  • Schein PS, Cooney DA, Vernon ML. The use of nicotinamide to modify the toxicity of streptozotocin diabetes without loss of antitumor activity. Cancer Res. 1967 Dec;27(12):2324–2332. [PubMed]
  • Herr RR, Jahnke JK, Argoudelis AD. The structure of streptozotocin. J Am Chem Soc. 1967 Aug 30;89(18):4808–4809. [PubMed]
  • HALES CN, RANDLE PJ. Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963 Jul;88:137–146. [PMC free article] [PubMed]
  • Seltzer HS, Allen EW, Herron AL, Jr, Brennan MT. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest. 1967 Mar;46(3):323–335. [PMC free article] [PubMed]
  • Howell SL, Taylor KW. The acute pancreatic effect of alloxan in the rabbit. J Endocrinol. 1967 Apr;37(4):421–427. [PubMed]
  • Lundquist I, Rerup C. On the development of alloxan diabetes in mice. Eur J Pharmacol. 1967 Oct;2(1):35–41. [PubMed]
  • Porte D, Jr, Graber AL, Kuzuya T, Williams RH. The effect of epinephrine on immunoreactive insulin levels in man. J Clin Invest. 1966 Feb;45(2):228–236. [PMC free article] [PubMed]
  • Mansford KR, Opie L. Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotocin or by alloxan. Lancet. 1968 Mar 30;1(7544):670–671. [PubMed]
  • LAZAROW A, LIAMBIES J, TAUSCH AJ. Protection against diabetes with nicotinamide. J Lab Clin Med. 1950 Aug;36(2):249–258. [PubMed]
  • KAPLAN NO, GOLDIN A, HUMPHREYS SR, CIOTTI MM, STOLZENBACH FE. Pyridine nucleotide synthesis in the mouse. J Biol Chem. 1956 Mar;219(1):287–298. [PubMed]
  • Colwell JA, Lein A. Diminished insulin response to hyperglycemia in prediabetes and diabetes. Diabetes. 1967 Aug;16(8):560–565. [PubMed]
  • Cerasi E, Luft R. The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus. Acta Endocrinol (Copenh) 1967 Jun;55(2):278–304. [PubMed]
  • Ricketts HT, Cherry RA, Kirsteins L. Biochemical studies of "prediabetes". Diabetes. 1966 Dec;15(12):880–888. [PubMed]
  • Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest. 1967 Dec;46(12):1954–1962. [PMC free article] [PubMed]

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