Imatinib mesylate improves insulin sensitivity and glucose disposal rates in high-fat diet fed rats

Robert Hägerkvist , Leif Jansson , Nils Welsh (1)

1 Dept. of Medical Cell Biology

The aim of the present study was to investigate whether imatinib affects the insulin sensitivity and glucose disposal of high-fat fed rats. Sprague-Dawley rats were fed either a standard pelleted rat food or a high-fat (60%) diet for 8 weeks. During the ten last days of the high-fat diet regime rats were gavaged daily with 0, 50 or 100 mg/kg of imatinib. The higher dose of imatinib resulted in a decreased psoas fat pad weight of the high-fat treated rats. At euglycemic, hyperinsulinemic clamp conditions high-fat fed rats exhibited increased insulin concentrations and a decreased glucose disposal. The moderate dose of imatinib, but not the high, normalized insulin sensitivity and glucose disposal without affecting the glucose metabolism in control rats. The hepatic glucose production at both fasting and hyperinsulinemic conditions was only weakly affected by imatinib. We conclude that a moderate dose of imatinib efficiently counteracts high-fat induced peripheral insulin resistance and that further studies on the mechanisms by which imatinib increases insulin action in muscle and fat tissues might generate novel strategies for the treatment of Type 2 diabetes.

Mots clés: Medicine

Robert Hägerkvist, Leif Jansson, Nils Welsh. Imatinib mesylate improves insulin sensitivity and glucose disposal rates in high-fat diet fed rats. Clinical Science, 2007, 114 (1), pp.65-71. ⟨10.1042/CS20070122⟩. ⟨hal-00479377⟩