L-arginine and polyamine administration protect beta-cells against alloxan diabetogenic effect in Sprague-Dawley rats.
In the searching for new substances with the capacity to protect beta-cells from the toxic effects of alloxan, we evaluated the effect of L-arginine and the polyamines putrescine, spermidine and spermine in a murine experimental model of diabetes. Diabetes was induced by the i.p. injection of either 200 mg/kg (24-h experiments) or 120 mg/kg (12 days experiments) body weight. L-Arginine and polyamines were administered 10 min before or 10 min after alloxan administration, once its half-life had elapsed, respectively. In the 24-h study, serum glucose (199.8+/-27.6 mg/dl) and triglyceride (54.6+/-4.9 mg/dl) concentrations showed a protective effect of spermine, as these parameters were not too high (P < or = 0.05), compared to the alloxan-treated group (415.4+/-47.8 and 90.2+/-11.6 mg/dl, respectively), and were closer to glucose (132.3+/-6.0 mg/dl) and similar to triglycerides (63.8+/-7.1 mg/dl) of the control group. A similar pattern was observed on the parameters measured when L-arginine and polyamines were administered daily for 12 days, starting 10 min after a single alloxan administration, which provides evidence that L-arginine and polyamines are effective in impeding the increase in serum glucose, triglyceride and cholesterol concentration showed on day 3 by the alloxan-treated group, as well as a higher acinar cell regenerative capacity as determined by immunohistochemical techniques. Spermine turning out to be more effective than L-arginine, putrescine or spermidine in counteracting the marked hyperglycemia and triglyceridemia showed by the alloxan-treated group and similar in effect when evaluating cholesterolemia. These results show a clear protective role of L-arginine and polyamines over the pancreatic beta-cell, in addition to the induction of neogenesis from both ductal and acinar cells that leads to the recovery of endocrine pancreatic function in rats with experimental diabetes.
Medical Research Unit in Metabolic Diseases, National Medical Center, Mexican Institute of Social Security, P.O. Box A-047, Mexico City, 06703 D.F., Mexico. mendezf@servidor.unam.mx
José D
JD
Méndez
Roberto De Haro
Rde H
Hernández
D000496:Alloxan / Q000633:toxicity; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004334:Drug Administration Schedule; D007120:Immunochemistry / Q000379:methods; D007274:Injections, Intraperitoneal; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011073:Polyamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D011073:Polyamines; D014280:Triglycerides; D000496:Alloxan; D001120:Arginine; D002784:Cholesterol; D001973:Bromodeoxyuridine