To compare the long-term effectiveness of whole
pancreas transplantation and pancreatic islet
transplantation in controlling the metabolic disorders of
alloxan diabetes, metabolic studies were performed monthly for 2 years in 4 groups of highly inbred rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated
alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants shortly after induction of diabetes with
alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500, but usually 2000, syngeneic pancreatic islets shortly after induction of diabetes with
alloxan. Whole
pancreas transplantation maintained strict metabolic control throughout the 2 years of study. In group
PDT,
hyperglycemia was abolished; plasma
glucose concentration was maintained tightly within the normal range; markedly depressed plasma
insulin levels were raised to above normal;
glucose tolerance tests had
insulin levels above normal and
glucose levels that increased less and declined more rapidly than normal; and
body weight gain and growth approached normal. In contrast, pancreatic islet
transplantation failed to maintain precise metabolic control. In group IT, plasma
glucose concentration initially fell to normal but then was elevated significantly above normal beginning with the 3rd posttransplant month; plasma
insulin level declined progressively after the 6th posttransplant month;
glucose tolerance tests had a diabetic
glucose tolerance curve as a result of a markedly deficient plasma
insulin response; and
body weight gain and growth were significantly less than in group
PDT. The results of these long-term metabolic studies may explain the effectiveness of whole
pancreas transplantation and the ineffectiveness of pancreatic islet
transplantation in preventing
diabetic nephropathy.