Preferential release of proinsulin relative to insulin in non-insulin-dependent diabetes mellitus.

A radioimmunoassay, using an antiserum that is specific for human proinsulin, has been used to study the response of serum proinsulin to low (25 g) and high (75 g) oral glucose loads in non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Diabetic patients were treated by diet only (N = 8) or were receiving oral anti-hyperglycemic agents (N = 8) and therapy was not interrupted during the study. In the fasted state, proinsulin concentrations were higher (P less than 0.05) in the drug-treated patients (31 +/- 3 pmol/l (SEM)) compared with age- and weight-matched healthy subjects (22 +/- 2 pmol/l; N = 10), but concentrations in the diet-treated patients 25 +/- 3 pmol/l) were not significantly different. Following 25 g and 75 g glucose loads, the rises in serum immunoreactive insulin and C-peptide concentrations in both groups of diabetic patients were impaired and delayed relative to those in the control subjects. The responses of serum proinsulin, however, were not significantly different in the NIDDM patients compared with controls at any time point up to 180 min except in the case of drug-treated patients receiving 25 g of glucose who had elevated (P less than 0.05) proinsulin concentrations at 150 min and 180 min after ingestion. It is concluded that NIDDM is not associated with an exaggerated release of proinsulin in response to glucose compared with healthy subjects, but the islets have maintained the ability to release proinsulin better than the ability to release insulin.