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December 24, 1955

CLINICAL EVALUATION OF LENTE INSULIN IN ONE HUNDRED NINE DIABETIC PATIENTS

JAMA. 1955;159(17):1611-1618. doi:10.1001/jama.1955.02960340031008
Abstract

The first significant advance in insulin modifications since the introduction of isophane (NPH) insulin, a crystalline modification of protamine zinc insulin, was the development of so-called insulin-zinc suspensions by Hallas-Møller and co-workers of the Novo Laboratories, Copenhagen, in 1952.1 Indeed, the rather startling revelation that zinc alone is capable of extending the time-action curve of insulin had eluded competent investigators for many years, simply because it was not fully realized that such delayed action is actually a fourfold function of a suitable buffer (acetate), a critical pH range (pH 5-8), the quantity of zinc present (not less than 0.5 mg. of zinc per 1,000 units of insulin), and the physical state of the insulin (amorphous and crystalline [large or small crystals]).

The commonly used phosphate buffer has been the major deterrent to prolongation of insulin action by zinc alone, even in the presence of large concentrations of zinc. In

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