The aim of the present study was to determine the influence of the venous drainage site on
insulin homeostasis and the possible risk for
atherosclerosis development after
pancreas transplantation. We studied inbred rats that received pancreas transplants with either systemic (STX) or portal (PTX) venous drainage after prior induction of diabetes with
streptozotocin and
sham-operated controls. The observation period was 6 months. Fasting plasma
glucose and
insulin levels were similar in all 3 groups, but fasting plasma
glucagon levels were elevated in STX (mean +/- SEM, 282+/-35 ng/L) in comparison to PTX rats (119+/-9 ng/L, P < .05), although the difference versus the control group (191+/-31 ng/L) was insignificant.
Glucose utilization and hepatic
glucose production (HGP), assessed by a dose-response euglycemic-hyperinsulinemic clamp in combination with tritiated
glucose infusion, were similar in all 3 groups. The groups were also similar with respect to the molar ratio of plasma
C-peptide and
insulin during basal steady state and the metabolic clearance rate (MCR) of
insulin during the clamp studies, suggesting an unchanged hepatic
insulin extraction (HIE) after
transplantation with either technique. Factors known to be related to
atherosclerosis, ie, blood pressure, intracellular
magnesium, and fasting levels of plasma
cholesterol,
triglycerides, and
high-density lipoprotein (HDL) and
low-density lipoprotein (
LDL) cholesterol, were similar in all 3 groups. Light microscopy of the aorta showed a slightly thicker intima in STX rats (24.3+/-0.5 microm, P < .05) versus PTX rats (21.4+/-0.7 microm) and control (21.4+/-0.6 microm); however,
atherosclerosis-like lesions were absent in all 3 groups. In conclusion, in a rat model with
streptozotocin-diabetes and
pancreas transplantation but no need for immunosuppression, both systemic and portal venous drainage avoid peripheral and hepatic
insulin resistance; also, there is no increased risk for
atherosclerosis.