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Horm Metab Res 2008; 40(4): 269-275
DOI: 10.1055/s-2007-1022546
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

A Novel Insulin Sensitizer (S15511) Enhances Insulin-stimulated Glucose Uptake in Rat Skeletal Muscles

N. Jessen 1 , E. Selmer Buhl 1 , 2 , R. Pold 1 , 2 , O. Schmitz 1 , 2 , S. Lund 1
  • 1Medical Research Laboratory and Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus C, Denmark
  • 2Institute of Clinical Pharmacology, University of Aarhus, Aarhus C, Denmark
Further Information

Publication History

received 20.04.2007

accepted 24.09.2007

Publication Date:
05 March 2008 (online)

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Abstract

Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

Key words

insulin sensitivity - type 2 diabetes - skeletal muscle - insulin sensitizer - GLUT4 - Wistar rat - insulin signaling

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Correspondence

N. JessenMD, PhD 

Medical Research Laboratory and Medical Department M (Endocrinology and Diabetes)

Aarhus University Hospital

8000 Aarhus C

Denmark

Phone: +45/89/49 16 15

Fax: +45/89/49 21 50

Email: Niels.Jessen@ki.au.dk