Is the combination of Β3-AR agonist and PPAR agonists a better treatment of type II diabetes and obesity?

  • RA Ngala
  • C Stocker
  • JRS Arch
  • MA Cawthorne
Keywords: b-AR, Beta-adrenoceptor PPAR-d Peroxisome Proliferator-Activated delta, HPMC Hydroxypropyl- methylcellulose

Abstract

Metabolic syndrome consists of insulin resistance, dyslipidaemia, obesity among other metabolic defects. Treatment of diabetes/obesity goes beyond glycaemic control. Effective management of diabetes involves the improvement of insulin sensitivity, regulation of body weight and improve-ment of lipid profile. However, there are very few drugs that are able to control more than one or two of these metabolic defects. This work is therefore aimed at studying the effect of a combina-tion of two potential antidiabetic agents in comparasm to the effects of the individual agent. Obese mice were treated (p.o) with 10mg/kg GW-800644 for 14 days. Dosing was twice daily at 9.00 and 17.00 hours. After 13 days of dosing, energy expenditure was measured, for three hours and then mice, were dosed with BRL-37344 (1mg/kg, i.p) and measurement continued for another six hours at room temperature (25.5oC). Plasma, glucose, insulin, triglycerides and non-esterified fatty acids were measured after individual treatment and after the combination treat-ment where possible. Energy expenditure was not significantly increased after treatment with GW80064 alone but was increased by 45% when combined with BRL37344. Insulin sensitivity was improved by 31% with GW80064 alone but by 41% in combination with BRL37344 with a corresponding decrease in plasma glucose. There was a significant improvement in the lipid pro-file even with the individual agonist. Therefore, the combination of β3-AR agonist and PPAR agonists would server a better treatment of type II diabetes and obesity than the individual agonist.
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