Glucose dose-relations of the early and late insulin responses were established in control, prediabetic and mildly diabetic subjects by performing glucose infusions with varying doses in each subject. Our earlier demonstration that the dose-response curves for both the early and late insulin responses are shifted toward the high glucose region in prediabetes and diabetes was confirmed. In a second series of experiments, a thirty minute arginine infusion was given fifty minutes before the start of the glucose infusion. The insulin response to arginine was reduced in the prediabetics and diabetics. Plasma insulin returned to base line at the start of the glucose infusion in the controls and prediabetics, but not in the diabetics. The early insulin response to glucose infusion was markedly enhanced by pretreatment with arginine at all glucose doses used, both in the controls and the prediabetics, whereas the late response was not modified. The results in the patients with mild diabetes were not conclusive. In the controls and prediabetics, the glucose-insulin dose-response curves for the early response were steeper after pretreatment with arginine. The percentile increase in insulin response was fairly constant throughout the range of hypergly-cemia induced. The insulinogenic index was increased by arginine with a factor of around 2 in controls as well as prediabetics, regardless of the dose of glucose administered.
These results, together with data reported previously by our group, indicate that arginine acts on insulin secretion by magnifying, at a constant rate, the insulinogenic signal of glucose. In prediabetics (and probably also in persons with slight diabetes), in whom the insulinogenic signal of glucose on the β-cell is diminished, arginine exerts quantitatively a similar degree of amplification. Therefore, it seems reasonable to assume that the mechanisms which mediate the amplifying effect of arginine in the β-cell are not deranged in prediabetes.