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Eur J Pharmacol ; 529(1-3): 172-8, 2006 Jan 04.
Article in English | MEDLINE | ID: mdl-16325798

ABSTRACT

In diabetic patients, impairment of wound healing is a serious problem which represents a significant health burden. The effect of a highly selective beta-3 adrenoceptor agonist, SR58611A, on wound healing was assessed in animal models of type II diabetes. In db/db diabetic mice, a daily oral treatment with SR58611A (1, 3 and 10 mg/kg/day for two weeks) significantly reduced hyperglycaemia from 3 mg/kg/day onwards. The compound also normalized wound healing, starting from the lowest dose tested (1 mg/kg/day). SR58611A did not affect wound healing of control (lean) mice. An oral anti-diabetic agent, devoid of affinity for beta-3 adrenoceptors, troglitazone (130 mg/kg/day p.o.), normalized glycaemia but did not improve wound healing in db/db mice. Local application of SR58611A (200 microg/day in db/db mice) did not affect wound healing. SR58611A also normalized glucose levels in ob/ob mice, but only slightly improved wound healing in this strain. Moreover, in 17-week old db/db mice (i.e. severely insulin resistant) and in streptozotocin-induced diabetic mice, SR58611A slightly decreased hyperglycaemia and did not affect wound healing. In conclusion, SR58611A improves wound healing in animal models of non-insulin-dependent diabetes. This effect is not related to its effect on glucose levels, but probably implicates systemic effects of the compound.


Subject(s)
Adrenergic beta-3 Receptor Agonists , Adrenergic beta-Agonists/therapeutic use , Diabetes Mellitus, Experimental/physiopathology , Obesity/physiopathology , Tetrahydronaphthalenes/therapeutic use , Wound Healing/drug effects , Administration, Oral , Adrenergic beta-Agonists/administration & dosage , Adrenergic beta-Agonists/pharmacology , Animals , Blood Glucose/analysis , Diabetes Mellitus, Experimental/metabolism , Male , Mice , Mice, Inbred C57BL , Obesity/metabolism , Skin/drug effects , Skin/injuries , Skin/pathology , Tetrahydronaphthalenes/administration & dosage , Tetrahydronaphthalenes/pharmacology , Time Factors
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