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

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 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.

journal_name

Diabetes

journal_title

Diabetes

authors

Mezza T,Ferraro PM,Sun VA,Moffa S,Cefalo CMA,Quero G,Cinti F,Sorice GP,Pontecorvi A,Folli F,Mari A,Alfieri S,Giaccari A

doi

10.2337/db18-0279

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

2389-2396

issue

11

eissn

0012-1797

issn

1939-327X

pii

db18-0279

journal_volume

67

pub_type

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