Diabetes, Vol 34, Issue 6 536-540, Copyright © 1985 by American Diabetes Association

ARTICLES

Effect of sodium 2-chloropropionate on glucagon secretion in the rat

G Ribes, G Valette, JM Dalstein and MM Loubatieres-Mariani

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.
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