Abstract
The intestinal absorption of 125I-labelled palmitoyl insulin was examined following administration into in-situ closed large intestinal loops of rats. When mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system into intestinal loops, a marked increase in plasma radioactivity and a corresponding disappearance of residual radioactivity in the intestinal lumen were observed in the following rank order: Palins-2 greater than Palins-1 greater than native insulin. In addition, the derivatives were more stable than native insulin in the mucosal tissue homogenates of the large intestine. These results suggest that chemical modification of insulin with palmitic acid may not only increase the lipophilicity of insulin but also reduce its degradation, resulting in the increased transfer of insulin across the large intestinal mucous membrane. The linoleic acid-HCO 60 mixed micelles system did not have a significant effect on the large intestinal absorption of radioactivity associated with the lipophilic insulin analogues.
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