Preserved Insulin Secretion and Insulin Independence in Recipients of Islet Autografts

Transplantation of pancreatic islets, rather than whole pancreas, has been introduced as a treatment for diabetes mellitus. We studied five patients ranging in age from 12 to 37 years who had severe chronic pancreatitis for which they underwent total pancreatectomy followed by isolation and hepatic transplantation of their own islets. All patients had remained insulin-independent for 1 to 7 1/2 years after transplantation. The numbers of islets transplanted ranged from 110,000 to 412,000. Islet function was assessed by measuring the plasma insulin responses to intravenous glucose and arginine and the plasma glucagon responses to hypoglycemia and arginine. In one patient, islet function was studied during catheterization of the hepatic vein, portal vein, and splenic artery and by analysis of a liver-biopsy specimen. After transplantation, the mean (±SD) fasting plasma glucose concentration was 122±47 mg per deciliter (6.8±2.6 mmol per liter) and the hemoglobin A_1c concentration was 6.0±0.8 percent in the five patients. The values were most abnormal — 214 mg per deciliter (11.9 mmol per liter) and 7.3 percent, respectively — in the patient who received only 110,000 islets. The acute plasma insulin responses to glucose and to arginine in the five patients were 23±13 and 26±10 μU per milliliter (168±94 and 184±70 pmol per liter), respectively, as compared with 58±6 and 37±8 μU per milliliter (416±44 and 267±61 pmol per liter) in the normal subjects. The peak plasma glucagon responses to insulin and arginine were 21±4 and 65±36 pg per milliliter, respectively, as compared with 125±28 and 156±99 pg per milliliter in the normal subjects. All five patients had plasma epinephrine but not pancreatic polypeptide responses to hypoglycemia. The results of the hepatic-vein catheterization in one patient indicated that the transplanted islets released insulin and glucagon in response to arginine. Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide. Intrahepatic transplantation of as few as 265,000 islets can result in the release of insulin and glucagon at appropriate times and in prolonged periods of insulin independence. (N Engl J Med 1992;327: 220–6.), THE amelioration of diabetes mellitus by the transplantation of pancreatic islets in animals has generated enthusiasm for the use of this procedure in humans with diabetes mellitus. If successful, islet transplantation would have advantages over transplantation of the entire pancreas. The procedure is shorter and easier, and the use of islets alone avoids the problem of exocrine drainage presented by the pancreatic allograft. However, there are only a few reports of transient successful transplantation of cadaveric islets in humans,^{1 2 3 4 5} and information about the secretion of hormones by the islets after successful transplantation is scant. Do the various types of islet…