Effect of venous drainage site on insulin action after pancreas transplantation in the rat--is there insulin resistance and a risk for atherosclerosis?
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.
Kissler
H J
HJ
Department of Surgery, University of Erlangen, Germany.
Gepp
H
H
Tannapfel
A
A
Schwille
P O
PO
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000601:surgery*; D004322:Drainage; D015309:Glucose Clamp Technique; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008297:Male; D016035:Pancreas Transplantation; D011169:Portal Vein; D011184:Postoperative Period; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D016042:Transplantation, Heterotopic; D014680:Veins
D001786:Blood Glucose; D007328:Insulin