Increased β-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans.

Mezza, Teresa; Ferraro, Pietro M.; Sun, Vinsin A.; Moffa, Simona; Cefalo, Chiara M. A.; Quero, Giuseppe; Cinti, Francesca; Sorice, Gian Pio; Pontecorvi, Alfredo; Folli, Franco; Mari, Andrea; Alfieri, Sergio; Giaccari, Andrea

Increased proinsulin secretion, which characterizes type 2 diabetes and insulin resistance, may be due to an intrinsic, primitive defect in proinsulin processing or be secondary to increased demand on β-cells (hyperinsulinemia secondary to insulin resistance). An alternative way to investigate the relation between relative hyperproinsulinemia and increased secretory demand is to study the dynamic changes in the proinsulin-to-insulin ratio after partial pancreatectomy, a model of acute increased β-cell workload on the remaining pancreas. To pursue this aim, patients without diabetes, scheduled for partial pancreatectomy, underwent 4-h mixed-meal tests and hyperinsulinemic-euglycemic clamps before and after surgery. After acute β-cell mass reduction, no changes were observed in the fasting proinsulin-to-insulin ratio, whereas the fold change in the proinsulin-to-insulin ratio significantly increased over time after the meal. Further, our data demonstrate that whole-body insulin resistance is associated with underlying defects in proinsulin secretion, which become detectable only in the presence of increased insulin secretion demand.

PROINSULIN; TYPE 2 diabetes; INSULIN resistance; HYPERINSULINISM; HYPOGLYCEMIA; PANCREATECTOMY; BLOOD sugar; COMPARATIVE studies; INSULIN; ISLANDS of Langerhans; LIPIDS; RESEARCH methodology; MEDICAL cooperation; RESEARCH; EVALUATION research; GLUCOSE clamp technique

Diabetes, 2018, Vol 67, Issue 11, p2389

0012-1797

Academic Journal

10.2337/db18-0279