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

Francesca Urbano1, Antonino Di Pino1, Roberto Scicali1

  • 1Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.

European Journal of Endocrinology
|September 24, 2019
PubMed
Abstract

Insights

Statin therapy in prediabetic individuals impairs glucagon suppression and reduces insulin sensitivity. This study reveals a molecular mechanism linking atorvastatin to altered insulin signaling in pancreatic alpha cells.

Area of Science:

  • Endocrinology
  • Metabolic Syndrome
  • Pharmacology

Background:

  • Statin therapy is associated with increased type 2 diabetes risk in high-risk populations.
  • The underlying pathophysiology linking statins to diabetes remains unclear.
  • Prediabetes is a critical stage for intervention and understanding metabolic alterations.

Purpose of the Study:

  • To investigate the effect of atorvastatin on glucagon suppression in prediabetic subjects.
  • To examine the relationship between glucagon suppression, insulin resistance, and statin therapy.
  • To explore the molecular mechanisms of insulin signaling in pancreatic alpha cells exposed to atorvastatin.

Main Methods:

  • Oral glucose tolerance test in 50 prediabetic subjects (26 on atorvastatin, 24 controls).
  • Evaluation of early, late, and overall glucagon suppression (0-120 min).
  • In vitro study of pancreatic alphaTC1-6 cells treated with atorvastatin to assess insulin signaling.

Main Results:

  • Atorvastatin users showed significantly reduced early (0-30 min) and overall (0-120 min) glucagon suppression.
  • Early glucagon suppression correlated significantly with statin therapy.
  • Impaired glucagon suppression was associated with lower insulin sensitivity (ISI0-120) and altered insulin signaling in alpha cells.

Conclusions:

  • Statin therapy in prediabetic patients leads to impaired glucagon suppression and reduced insulin sensitivity.
  • Atorvastatin exposure affects insulin-mediated glucagon suppression and key insulin signaling pathways in pancreatic alpha cells.
  • This study elucidates a novel molecular mechanism contributing to statin-induced insulin resistance.

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