{beta}-Cell function following human islet transplantation for type 1 diabetes.
Islet transplantation can provide metabolic stability for patients with type 1 diabetes; however, more than one donor pancreas is usually required to achieve insulin independence. To evaluate possible mechanistic defects underlying impaired graft function, we studied five subjects at 3 months and four subjects at 12 months following intraportal islet transplantation who had received comparable islet equivalents per kilogram (12,601 +/- 1,732 vs. 14,384 +/- 2,379, respectively). C-peptide responses, as measures of beta-cell function, were significantly impaired in both transplant groups when compared with healthy control subjects (P < 0.05) after intravenous glucose (0.3 g/kg), an orally consumed meal (600 kcal), and intravenous arginine (5 g), with the greatest impairment to intravenous glucose and a greater impairment seen in the 12-month compared with the 3-month transplant group. A glucose-potentiated arginine test, performed only in insulin-independent transplant subjects (n = 5), demonstrated significant impairments in the glucose-potentiation slope (P < 0.05) and the maximal response to arginine (AR(max); P < 0.05), a measure of beta-cell secretory capacity. Because AR(max) provides an estimate of the functional beta-cell mass, these results suggest that a low engrafted beta-cell mass may account for the functional defects observed after islet transplantation.
Rickels
Michael R
MR
University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes,Metabolism, 778 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104-6149, USA. mrrickels@aol.com
Schutta
Mark H
MH
Markmann
James F
JF
Barker
Clyde F
CF
Naji
Ali
A
Teff
Karen L
KL
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D002149:Energy Intake; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide