Proglumide, a cholecystokinin receptor antagonist, exacerbates alloxan-induced diabetes mellitus in Swiss mice

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Abstract
The effect of proglumide ((±)-4-benzamido-N,N-dipropylglutaramic acid), a gastrin and cholecystokinin receptor antagonist, has been studied on the fasting plasma glucose (FPG) and insulin levels in normal and alloxan-diabetic mice. In normal mice, proglumide, administered as a single oral dose or twice daily for five consecutive days, did not produce any alteration in those parameters. Injection of alloxan monohydrate (70 mg kg−1 i.v.) produced a significant decrease in plasma insulin and a significant elevation of FPG levels on the 5th day after its administration as evidence of diabetes mellitus. Proglumide sodium, given as a single acute dose on the 5th day of alloxan injection, or as a twice daily dose for 5 days immediately after alloxan injection, significantly exacerbated the hyperglycaemia and further decreased the plasma insulin levels thus worsening the diabetogenic effect of alloxan. These observations point to a possible involvement of cholecystokinin (CCK) in alloxan-induced diabetes and indicate a need for monitoring the levels of FPG in diabetic patients being treated with a high dose of proglumide or other CCK-antagonists.