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Impaired glucagon suppression and reduced insulin sensitivity in subjects with prediabetes undergoing atorvastatin therapy.

Abstract：

Objective:Statin therapy has been linked to an increased risk of type 2 diabetes in high-risk populations; however, the pathophysiology of this association remains to be clarified. We investigated glucagon suppression and its relationship with insulin resistance in prediabetic subjects undergoing atorvastatin therapy; in addition, we studied molecular insulin signaling in pancreatic α-cells exposed to atorvastatin in vitro. Design and methods:Fifty subjects with prediabetes were divided into two groups based on atorvastatin therapy. All subjects underwent an oral glucose tolerance test. Early (0-30 min), late (30-120 min) and overall (0-120 min) glucagon suppression were evaluated. Insulin sensitivity was estimated by the insulin sensitivity index (ISI0-120). Insulin signaling pathway and insulin-mediated glucagon suppression were investigated in pancreatic αTC1-6 cells chronically exposed (24 or 48 h) to atorvastatin (100 ng/mL). Results:Individuals on statin therapy (n = 26) showed a significantly reduced early (0-30 min) (P = 0.003) and overall (0-120 min) (P = 0.01) glucagon suppression compared with controls (n = 24). In multivariate regression analysis, early glucagon suppression (0-30 min) exhibited a significant correlation with statin therapy. Regression analysis showed a significant association between ISI 0-120 and early0-30 (r = 0.33, P < 0.05) and overall0-120 (r = 0.38, P < 0.05) glucagon suppression. Moreover, in αTC1-6 cells atorvastatin treatment affected insulin-mediated glucagon suppression, insulin receptor phosphorylation and IRS-1-AKT pathway signaling. Conclusions:Prediabetic patients undergoing statin therapy exhibit impaired glucagon suppression associated with lower insulin sensitivity. Our data revealed a new molecular aspect behind the deregulation of insulin sensitivity secondary to statin exposure.

journal_name

Eur J Endocrinol

journal_title

European journal of endocrinology

authors

Urbano F,Di Pino A,Scicali R,Filippello A,Di Mauro S,Scamporrino A,Marchisello S,Rabuazzo AM,Purrello F,Piro S

doi

10.1530/EJE-19-0173

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

579-590

issue

eissn

0804-4643

issn

1479-683X

pii

EJE-19-0173.R2

journal_volume

181

pub_type

杂志文章

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Impaired glucagon suppression and reduced insulin sensitivity in subjects with prediabetes undergoing atorvastatin therapy.