Summary
The purpose of this investigation was to ascertain the ability of phenazine methosulfate (PMS) to improve the streptozotocin (STZ) and alloxan induced diabetic conditionin vivo as determined by changes in blood and urine glucose levels and by alteration in the secretion of insulin by isolated islets. STZ and alloxan diabetes was induced in male albino rats (200–250 g body weight). A single injection of PMS (6.0 mg/kg) or nicotinamide (500 mg/kg) simultaneously with diabetic doses of either STZ or alloxan caused a significant reduction in blood and urine glucose levels three days after the injection. The reduction in glycemic levels was greater with PMS than with nicotinamide. Daily PMS (0.5 mg/kg) injection, initiated 5, 10, 20 or 30 days after the development of STZ- and alloxan-diabetes, caused a significant decrease in blood and urine glucose levels and also increased body weight determined 60 days after STZ or alloxan administration. These effects were observed even if the injections were initiated 20 or 30 days after the onset of the diabetic syndrome. Glucose stimulated insulin secretion was significantly inhibited by pre-incubation of isolated islets for one hour at 37 °C with either STZ or alloxan. However, insulin secretion was induced by PMS in the STZ or alloxan pretreated islets. Nicotinamide neither protected nor induced insulin secretion under similar conditions. The level of insulin secretion induced by PMS whether in the normal islets or in islets previously exposed to the B-cytotoxic agents were comparable in quantity to glucose (17 mM)-stimulated insulin secretion. Data presented in this study are suggestive evidence for the potentiality of a reactive proton donor as an insulin secretagoguein vivo andin vitro.
Similar content being viewed by others
References
Akpan J. O.: The characterization of the protection by nicotinamide against the action of diabetogenic nitrosoureas — Diabète Métabol.14, 693–699, 1988.
Akpan J. O., Wright P. H., Pulin W. E.: Effect of diabetogenic nitrosourea on the activity of the pentose phosphate shunt in isolated islets — Acta diabetol. lat.19, 37–47, 1982.
Akpan J. O., Wright P. H., Dulin W. E.: The characterization of phenazine methosulfate stimulated insulin secretion — Acta diabetol. lat.24, 65–78, 1987.
Ammon H. P. T., Steinke J.: 6-Aminonicotinamide (6-AN) as a diabetogenic agent.In vitro andin vivo studies in the rat — Diabetes21, 143–148, 1972.
Ho Chen-Kung, Hashim S. A.: Pyridine nucleotide depletion in pancreatic islets associated with streptozotocin-induced diabetes — Diabetes21, 789–793, 1972.
Kun E., Langer B., Urlich B., Holzer H., Grnicke H.: The role of DPNase in the mechanisms of action of an antitumor alkylating agent on Ehrlich ascites cells — Proc. nat. Acad. Sci. (Wash.)52, 1501–1506, 1956.
Lacy P. E., Kostianovsky M.: Method for the isolation of intact islets of Langerhans from the rat pancreas — Diabetes16, 35–39, 1967.
Makulu D. R., Vichick D., Wright P. H., Sussman K. E., Yu P. L.: Insulin immunoassay by back-titration using alcohol precipitation of insulin antibody complexes — Diabetes18, 660–669, 1969.
Malaisse W. J.: Alloxan toxicity to the pancreatic beta cell: a new hypothesis — Biochem. Pharmacol.31, 3527–3534, 1982.
Malaisse W. J., Malaisse-Lagae F., Sener A., Pipeleers D. G.: Determinants of the selective toxicity of alloxan to the pancreatic beta cell — Proc. nat. Acad. Sci. (Wash.)79, 927–930, 1982.
Mcilwan H.: Properties of preparations from the central nervous system which degrade coenzymes I and II, their connection with carbohydrate metabolism — Biochem. J.46, 612–619, 1950.
Schein P. S., Loftus S.: Streptozotocin: depression of mouse liver pyridine nucleotides — Cancer Res.28, 1501–1506, 1968.
Yamamoto H., Uchigata Y., Okamoto H.: Streptozotocin and alloxan induce DNA strand breaks and poly (ADP-ribose) synthetase in pancreatic islets — Nature (Lond.)294, 284–286, 1981.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Akpan, J.O. Reduction in blood and urine glucose levels in streptozotocin and alloxan diabetes by phenazine methosulfate. Acta diabet. lat 26, 195–201 (1989). https://doi.org/10.1007/BF02581385
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02581385