Increased B-cell workload modulates proinsulin-to-insulin ratio in humans

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

Research output: Contribution to journalArticle

Abstract

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 b-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 b-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 b-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.

Original languageEnglish
Pages (from-to)2389-2396
Number of pages8
JournalDiabetes
Volume67
Issue number11
DOIs
Publication statusPublished - Nov 1 2018

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Mezza, T., Ferraro, P. M., Sun, V. A., Moffa, S., Cefalo, C. M. A., Quero, G., Cinti, F., Sorice, G. P., Pontecorvi, A., Folli, F., Mari, A., Alfieri, S., & Giaccari, A. (2018). Increased B-cell workload modulates proinsulin-to-insulin ratio in humans. Diabetes, 67(11), 2389-2396. https://doi.org/10.2337/db18-0279