Influence of portal delivery of insulin on intracellular glucose and lipid metabolism

Abstract

We have investigated whether portal delivery of insulin as a result of intrahepatic islet cell autografts would prevent the development of metabolic alterations. Seven pancreatectomized dogs received islet autografts transplanted into the liver through the portal vein (PD). One year after transplantation, their intravenous glucose tolerance and insulin responses were similar to age-matched control (C) dogs (n = 5). Also, normal triglyceride content in arterial smooth muscle and striated muscle was observed in the dogs with portal insulin delivery in contrast to the substantial increases we observed in pancreatectomized dogs (n = 7) with pancreatic autografts that drained into the systemic circulation (SD). In these dogs, the tissue samples were taken at the age of 3 to 4 years. Triglyceride content (mean ± SEM) in the aorta was 4.9 ± 1.2 versus 2.6 ± 0.6 versus 20.7 ± 8.0 μmol/g ( P < .01) in C, PD, and SD models, respectively. The corresponding values for triglyceride content in striated muscles were 29.1 ± 1.2, 25.9 ± 1.5, and 171.4 ± 46.6 μmol/g ( P < .01). Glucose-6-phosphate dehydrogenase (G-6-PDH) and malic enzyme, key enzymes for lipid synthesis, were also normal in the PD model, in contrast to the fivefold increased activity of these enzymes in the SD model ( P < .01). The glycolytic enzymes, hexokinase (HK) and phosphofructokinase (PFK), were normal compared with the decreased values in the SD. These data indicate that it is possible to normalize glucose and lipid metabolism in arterial walls by portal delivery of insulin, following intrahepatic islet cell transplantation. The portal delivery of insulin may, ultimately, be shown to be uniquely advantageous in reducing lipid-related risk factors for macroangiopathy in patients with diabetes mellitus.