PROINSULIN, C-PEPTIDE, AND INSULIN IN NORMAL SUBJECTS DURING AN 8-H HYPERGLYCEMIC CLAMP

Increased concentrations of proinsulin immunoreactive material (PIM) a bsolutely or relative to insulin is a characteristic finding in patien ts with non-insulin-dependent diabetes mellitus (NIDDM). The aim of th is study was to test if 8 h or mild hyperglycemia (7-9 mmol/l) in heal thy subjects could induce a preferential secretion of PIM from B cells . Serum concentrations of insulin, C-peptide and PIM were measured eve ry 10 min during the 8 h of continuous glucose infusion in nine normal -weight healthy subjects without diabetes among their first-degree rel atives, After a gradual rise in B-cell peptides, a steady state was re ached. From 4 to 8h no further difference in insulin, C-peptide or PIM concentration was found. Fasting PIM/C-peptide and PIM/insulin ratios of 0.5% and 2.3% increased during the glucose clamp to levels of 1.4% and 7.6%, respectively, Neither testing the regression slope nor comp aring individual time points showed any significant difference for the PIM/C-peptide ratio from 2 to 8 h and for the PIM/insulin ratio from 3 to 8 h. These results do not support the hypothesis that an increase d glucose drive per se results in an altered B-cell function with incr easing PIM/C-peptide ratio, At least 8 h of mild hyperglycemia in heal thy subjects does not progressively alter B-cell function.