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.

Increased B-cell workload modulates proinsulin-to-insulin ratio in humans / 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.. - In: DIABETES. - ISSN 0012-1797. - 67:11(2018), pp. 2389-2396. [10.2337/db18-0279]

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

Cefalo C. M. A.;
2018

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.
2018
insulin secretion; type 2 diabetes; insulin-resistance
01 Pubblicazione su rivista::01a Articolo in rivista
Increased B-cell workload modulates proinsulin-to-insulin ratio in humans / 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.. - In: DIABETES. - ISSN 0012-1797. - 67:11(2018), pp. 2389-2396. [10.2337/db18-0279]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1675043
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