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Effects of novel beta-adrenoceptor agonists on carbohydrate metabolism: relevance for the treatment of non-insulin-dependent diabetes

, : Effects of novel beta-adrenoceptor agonists on carbohydrate metabolism: relevance for the treatment of non-insulin-dependent diabetes. International Journal of Obesity 8 Suppl 1: 93-102

BRL 26830A, (R*, R*)-(+/-)-methyl 4-[2-[(2-hydroxy-2-phenylethyl) amino] propyl]-benzoate, (E)-2-butenedioate (2:1) salt, is a new antihyperglycemic agent orally active in obese-hyperglycemic animal models. In C57Bl/6 ob/ob mice, BRL 26830A (1 mg/kg) given daily for periods of 14 d-6 weeks produced a marked improvement in glucose tolerance and a reduction in the fasting plasma insulin concentration. Adipocytes prepared from treated mice showed improved insulin responsiveness. In Zucker fa/fa rats, treatment with BRL 26830A (2.9 mg/kg/d for 23 d) produced improvements in both glucose tolerance and whole animal insulin sensitivity, as assessed by rate of fall of blood glucose in response to an intravenous dose of insulin. In C57Bl/KSJ db/db mice, BRL 26830A (admixed with food at 50 mg/kg diet) decreased blood glucose to values similar to those in lean mice. At the end of a 10-week treatment, BRL 26830A-treated mice had a higher plasma and pancreatic insulin content than the untreated db/db mice. In normoglycaemic rats and mice, BRL 26830A increases the plasma insulin concentration and increases glucose disposal. However, in most circumstances, there is a counteracting increase in endogenous glucose synthesis and, therefore, no change in blood glucose occurs. Improvements in glucose tolerance occur in 24-h fasted rats and mice. BRL 26830A has thermogenic activity and it is suggested that this might be linked to increased glucose utilization. Brown adipose tissue (BAT) of C57Bl/KSJ db/db mice has a reduced maximum glycolytic capacity relative to lean littermates. Treatment with BRL 26830A increased the glycolytic capacity 10-fold.


PMID: 6152558

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