Glucose-infusion tests were performed on patients admitted for elective upper abdominal surgery 1 day before and 1 day after operation. In addition to insulin and proinsulin, a third immunoreactive insulin species of mol. wt. 20 000--30 000 was detected in plasma from two patients. The heterogeneity of plasma immunoreactive insulin (IRI) and the need to consider the effects of all forms, including proinsulin and the high-molecular-weight species, is emphasized. 2. During preoperative glucose infusions there was an increase in the percentage of the total plasma IRI present as high-molecular-weight forms (i.e. proinsulin plus the species of mol. wt. 20 000--30 000) from 3.9% to 10.8%. On the first postoperative morning all patients showed an increase in the amounts of the heavier IRI types, which accounted for 13.9% of the total plasma IRI. 3. The changes in insulin and proinsulin are consistent with the release from the pancreas of an insulin/proinsulin mixture of constant proportions, and the longer circulating half-life of proinsulin. 4. Increases in the amounts of high-molecular-weight IRI species after surgery may have a partial role in the development of insulin resistance but are probably not a major determinant of the insulin-resistant state.
