Ammonium chloride potentiation of streptozotocin-induced diabetes in juvenile pigs

In preparation for direct vital microscopic evaluation of microcirculatory dynamics in the diabetic pig myocardium, we were initially unsuccessful in inducing sustained hyperglycemia in juvenile pigs using streptozotocin according to previously reported methods. Therefore, we modified the technique in a way previously unreported in an effort to improve the success rate of diabetes induction. In the first set of 9 pigs, we followed described methods of intravenous injection with 150 mg/kg streptozotocin. In the second group of 9, the technique was modified. The change was based on human studies with ammonium chloride and animal experiments with alloxan, and consisted of the addition of a period of pretreatment with ammonium chloride. Of the nine pigs not treated with ammonium chloride, only two developed sustained hyperglycemia in excess of 17 mmol/L (300 mg/dl), and only after reinjection with a full dose of streptozotocin within 7 days of the first injection. Conversely, of the ammonium chloride pretreated pigs, eight of nine developed diabetes. We conclude that the addition of ammonium chloride to produce systemic acidosis prior to streptozotocin injection improves the efficacy of the drug.