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Effect Of Charge On Hepatic Specific Nature Of Vesicle Encapsulated Insulin In Conscious Dogs.

R. S. Spangler, K. Triebwasser, M. L. Wilson
Published 1986 · Biology, Medicine

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Positively [(+)-VEI] and negatively [(-)-VEI] charged formulations of vesicle encapsulated insulin (VEI) were compared with insulin on the basis of their ability to suppress hepatic glucose production (hepatic Ra) and stimulate glucose utilization (Rd) in conscious dogs. Our results indicate that (-)-VEI and insulin have an equivalent capacity to suppress hepatic glucose production at dose levels of 0.2, 1.2, and 2.4 mU X kg-1 X min-1. (+)-VEI is less effective at suppressing hepatic Ra than both insulin and (-)-VEI at dose levels of 1.2 and 2.4 mU X kg-1 X min-1. Both (+)-VEI and (-)-VEI induced significantly less glucose utilization than a comparable amount of insulin at dose levels of 1.2 and 2.4 mU X kg-1 X min-1. The amount of glucose utilization stimulated by (+)-VEI was significantly less than that induced by insulin at 0.6 mU X kg-1 X min-1. This difference was not evident with (-)-VEI. These results suggest that the insulin contained in (+)-VEI is less bioavailable than that contained in (-)-VEI. This difference in bioavailability is believed to be the result of greater serum stability of (+)-VEI vesicles when compared with that of (-)-VEI. In conclusion, both (+)-VEI and (-)-VEI have the capacity to shield encapsulated insulin from interacting with peripheral tissues and deliver insulin selectively to the liver. Both formulations afford one an opportunity to expand the therapeutic window for hepatically active compounds where their utility is limited by systemic toxicity.
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