Islet cell hormonal responses to hypoglycemia after human islet transplantation for type 1 diabetes.
Islet transplantation can eliminate severe hypoglycemic episodes in patients with type 1 diabetes; however, whether intrahepatic islets respond appropriately to hypoglycemia after transplantation has not been fully studied. We evaluated six islet transplant recipients, six type 1 diabetic subjects, and seven nondiabetic control subjects using a stepped hyperinsulinemic-hypoglycemic clamp. Also, three islet transplant recipients and the seven control subjects underwent a paired hyperinsulinemic-euglycemic clamp. In response to hypoglycemia, C-peptide was similarly suppressed in islet transplant recipients and control subjects and was not detectable in type 1 diabetic subjects. Glucagon was significantly more suppressed in type 1 diabetic subjects than in islet transplant recipients (P < 0.01), although the glucagon in islet transplant recipients failed to activate as in the control subjects (P < 0.01). Pancreatic polypeptide failed to activate in both type 1 diabetic subjects and islet transplant recipients compared with control subjects (P < 0.01). In islet transplant recipients, glucagon was suppressed normally by hyperinsulinemia during the euglycemic clamp and was significantly greater during the paired hypoglycemic clamp (P < 0.01). These results suggest that after islet transplantation and in response to insulin-induced hypoglycemia, endogenous insulin secretion is appropriately suppressed and glucagon secretion may be partially restored.
Rickels
Michael R
MR
Division of Endocrinology, Diabetes & Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6149, USA. rickels@mail.med.upenn.edu
Schutta
Mark H
MH
Mueller
Rebecca
R
Markmann
James F
JF
Barker
Clyde F
CF
Naji
Ali
A
Teff
Karen L
KL
D001786:Blood Glucose; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon