Effect of sodium 2-chloropropionate on glucagon secretion in the rat.
We have previously shown that, in alloxan-diabetic dogs, the adjunction of sodium 2-chloropropionate (2-CP) with insulin injections resulted in a reduction of both hyperglycemia and hyperglucagonemia. The present studies were designed to more closely examine the glucagon-lowering effect of 2-CP. We investigated whether 2-CP was able to reduce elevated glucagon secretion both in vivo in streptozocin (STZ)-diabetic rats, and in vitro in the isolated, perfused rat pancreas. 2-CP (1 mmol/kg or 108 mg/kg) was given during 2 mo through esophageal tube to diabetic rats deprived of exogenous insulin. The drug induced a significant reduction of hyperglucagonemia (P less than 0.05) of blood lactate and alanine levels (P less than 0.02) and of plasma triglyceride levels (P less than 0.001). Furthermore, 2-CP markedly decreased glucosuria (P less than 0.005). In the isolated rat pancreas perfused with 2.8 mmol/L glucose, the continuous perfusion of 2-CP (1 mmol/L) starting before an infusion of arginine or alanine (5 mmol/L) considerably reduced the hypersecretion of glucagon evoked by these amino acids (P less than 0.001). These experiments show that sodium 2-chloropropionate can reduce glucagon hypersecretion in the diabetic rat not only in vivo, but acts also directly in vitro on the isolated, perfused pancreas of normal rats.
D000409:Alanine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005934:Glucagon / Q000097:blood*; D006029:Glycosuria / Q000188:drug therapy; D006843:Hydrocarbons, Chlorinated; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D006843:Hydrocarbons, Chlorinated; D011422:Propionates; D005934:Glucagon; D001120:Arginine; C021974:2-chloropropionic acid; D000409:Alanine