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Sökning: L773:0143 5221 > Welsh Nils

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  • Hägerkvist, Robert, et al. (författare)
  • Imatinib mesylate improves insulin sensitivity and glucose disposal rates in rats fed a high-fat diet
  • 2008
  • Ingår i: Clinical Science. - 0143-5221. ; 114:1, s. 65-71
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  • Mokhtari, Dariush, et al. (författare)
  • Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes
  • 2010
  • Ingår i: Clinical Science. - 0143-5221. ; 118:3-4, s. 241-247
  • Tidskriftsartikel (refereegranskat)abstract
    • Altered tyrosine kinase signalling has been implicated in several diseases, paving the way for the development of small-molecule TKIs (tyrosine kinase inhibitors). TKIs such as imatinib, sunitinib and dasatinib are clinically used for treating chronic myeloid leukaemia, gastrointestinal stromal tumours and other malignancies. In addition to their use as anti-cancer agents, increasing evidence points towards an anti-diabetic effect of these TKIs. Imatinib and other TKIs counteract diabetes not only in non-obese diabetic mice, but also in streptozotocin diabetic mice, db/db mice, high-fat-treated rats and humans with T2D (Type 2 diabetes). Although the mechanisms of protection need to be investigated further, the effects of imatinib and other TKIs in human T2D and the rapidly growing findings from animal models of T1D (Type 1 diabetes) and T2D are encouraging and give hope to improved treatment of human diabetes. In the present article, we review the anti-diabetic effects of TKIs which appear to involve both protection against beta-cell death and improved insulin sensitivity. Considering the relatively mild side effects of TKIs, we hypothesize that TKIs could be used to treat new-onset T1D, prevent T1D in individuals at high risk of developing the disease, treat the late stages of T2D and improve the outcome of islet transplantation.
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  • Resultat 1-2 av 2
Typ av publikation
tidskriftsartikel (2)
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refereegranskat (2)
Jansson, Leif, (1)
Mokhtari, Dariush, (1)
Hägerkvist, Robert, (1)
Uppsala universitet (2)
Engelska (2)


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