Effect of SR58611A, a potent beta-3 adrenoceptor agonist, on cutaneous wound healing in diabetic and obese mice.
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.
Schaeffer
Paul
P
Cardiovascular Thrombosis Department, Sanofi-Synthélabo Recherche, 195 Route d'Espagne, 31036 Toulouse, France. paul.schaeffer@sanofi-aventis.com
Bernat
André
A
Arnone
Michele
M
Manara
Luciano
L
Gallas
Jean-François
JF
Dol-Gleizes
Frédérique
F
Millet
Laurence
L
Grosset
Alain
A
Herbert
Jean-Marc
JM
D000284:Administration, Oral; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D013764:Tetrahydronaphthalenes; C076252:amibegron