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.
Méndez
José D
JD
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
Hernández
Roberto De Haro
Rde H
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