Imatinib mesylate improves insulin sensitivity and glucose disposal rates in rats fed a high-fat diet.
The aim of the present study was to investigate whether imatinib affects insulin sensitivity and glucose disposal in HF (high-fat)-fed rats. Sprague-Dawley rats were fed either a standard pelleted rat food (low-fat diet) or an HF diet (60% fat) for 8 weeks. During the last 10 days of the HF diet regime, rats received saline alone or imatinib (50 or 100 mg/kg of body weight) daily by gavage. The higher dose of imatinib resulted in a decreased psoas fat pad weight in the HF-treated rats. Under euglycaemic hyperinsulinaemic clamp conditions, HF-fed rats exhibited increased insulin concentrations and decreased glucose disposal. The lower (50 mg/kg of body weight), but not the higher (100 mg/kg of body weight), dose of imatinib normalized insulin sensitivity and glucose disposal without affecting glucose metabolism in low-fat-fed rats. Hepatic glucose production at both fasting and hyperinsulinaemic conditions was only weakly affected by imatinib. We conclude that a moderate dose of imatinib efficiently counteracts HF-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.
Hägerkvist
Robert
R
Department of Medical Cell Biology, Uppsala University, S-75123 Uppsala, Sweden.
Jansson
Leif
L
Welsh
Nils
N
D000818:Animals; D001549:Benzamides; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D015309:Glucose Clamp Technique; D006400:Hematocrit; D000068877:Imatinib Mesylate; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000033:anatomy & histology; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001549:Benzamides; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate