Improvement of ketoacidosis in the diabetic rat after the administration of the oral antilipolytic agent GR 79236.
1. We assessed the effect of a novel oral antilipolytic agent, N-[(1S, trans)-2-hydroxycyclopentyl]adenosine (GR 79236), in experimental diabetic ketoacidosis. Ketotic rats were gavaged with GR 79236 (1 mg/kg) or water (vehicle) and their blood/plasma/serum biochemistry and haematological profile was determined. 2. We found that GR 79236 reduced the plasma non-esterified fatty acid concentration. This effect was associated with the correction of blood/plasma/serum biochemical variables (beta-hydroxybutyrate, acetoacetate, triacylglycerol) directly related to diabetic ketoacidosis, and of others (cholesterol, creatinine, creatine kinase and aspartate transaminase) which are not directly related to this metabolic abnormality. 3. There was, however, no evidence of GR 79236 lowering blood glucose in this model. One possible explanation for this observation is that GR 79236 stimulated gastric emptying leading to enhanced absorption of stomach contents when compared with untreated animals.
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital School of Medicine, London, U.K.
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Thompson
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Strong
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Mikhailidis
D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D016883:Diabetic Ketoacidosis / Q000097:blood / Q000188:drug therapy*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D019344:Lactic Acid; D000241:Adenosine; C082299:N-((1S,trans)-2-hydroxycyclopentyl)adenosine