**17. Bile acids as hypoglycemic agents**

Recent studies have shown that the semisynthetic bile acid analogue, 12-monoketocholic acid (MKC) exerted a significant hypoglycemic effect when administered alone to a rat model of T1D. When administered with insulin, MKC exerted a synergistic effect potentiating the hypoglycemic effect of insulin (Kuhajda et al. 2000; Mikov et al. 2008). MKC hypoglycemic effect was studied using various formulations including the oral, nasal, ocular and rectal applications. Then, the hypoglycemic effect was compared with that of insulin injected subcutaneously. The mixture of MKC and insulin also tested for hypoglycemic activity. Nasal administration of the insulin-MKC mixture resulted in a decrease of blood glucose concentration that reached 54% of that obtained after subcutaneous application of insulin. However, following nasal administration of the MKC, the decrease in blood glucose reached 36% of that obtained after subcutaneous application of insulin. The discovery of a link between bile acids and glucose regulation offers a new perspective in the design of hypoglycaemic drugs in treating diabetes (Miljkovic et al. 2000). The mechanisms by which, bile acids such as MKC exerts its hypoglycemic effect in T1D, was explored further. The hypoglycemic effect of bile acids on T1D rats could be explained through their effect on FXR and PPARs metabolic pathways (Houten et al. 2006b; Trauner et al. 2010). However such mechanisms remain to be fully characterized.
