Studies on pyrazinoylguanidine. 2. Comparative drug and dose effects on glucose and lipid metabolism in streptozotocin-induced diabetic rats.
In streptozotocin (STZ)-induced diabetic rats, pyrazinoylguanidine (PZG) markedly reduced elevated fasting concentrations of plasma glucose, triglycerides, and cholesterol. In contrast, these parameters were unaffected by a sulfonylurea, glyburide, or by a biguanide, metformin. PZG's glucose- and lipid-lowering effects were dose-dependent. These metabolic effects were also investigated after: (a) pyrazinoic acid (PZA), a metabolite of PZG; (b) 3-amino-PZG, an analog of PZG, and (c) 3-amino-PZA, a hydrolytic product of 3-amino-PZG. PZA moderately reduced elevated fasting glucose and lipid concentrations in STZ-diabetic rats, suggesting partial medication of PZG's antidiabetic actions by PZA. Neither 3-amino-PZG nor 3-amino-PZA exerted any glucose- or lipid-lowering effect in STZ-diabetic rats.
A-Rahim
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Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Beyer
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KH
Vesell
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ES
D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D006146:Guanidines; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D011719:Pyrazines; C056106:3-amino-2-pyrazinoylguanidine; D011718:Pyrazinamide; C005296:pyrazinoic acid; D013311:Streptozocin; C056104:2-pyrazinoylguanidine; D008687:Metformin; D005905:Glyburide