AJP - Endocrinology and Metabolism, Vol 249, Issue 2 152-E159, Copyright © 1985 by American Physiological Society
Selective insulinization of liver in conscious diabetic dogs
R. S. Spangler
Insulin encapsulated in lipid vesicles and targeted to hepatocytes by means
of a digalactosyl diglyceride moiety [(designated vesicle encapsulated
insulin (VEI)] was administered intravenously to conscious catheterized
diabetic dogs to determine the effects of hepatic and extrahepatic glucose
utilization. Our results indicate that VEI administered intravenously to
diabetic dogs over a dose range of 0.5 to 2.0 mU X kg-1 X min-1 reduces
hepatic glucose output or induces hepatic glucose uptake without causing
any significant alteration in the rate of extrahepatic glucose utilization.
Steady-state comparisons of 1.0 mU X kg-1 X min-1 VEI with intraportal and
peripherally administered insulin revealed that VEI and intraportal insulin
result in significantly less extrahepatic glucose utilization than does an
equivalent dose of peripherally administered insulin (6.36 +/- 1.21 and
5.08 +/- 0.97 vs. 8.82 +/- 1.61 mg X kg-1 X min-1; P less than 0.03).
Through the use of VEI, we were able to significantly alter the deposition
of intravenously administered glucose from 11% hepatic and 89% extrahepatic
noted with peripheral insulin to 35% hepatic and 65% extrahepatic with VEI
(P less than 0.03). Thus, by encapsulating insulin into a lipid carrier
specifically targeted to the liver, selective hepatic insulinization can be
achieved. As a result of this approach, one can alter the distribution of a
glucose load to favor hepatic deposition.
