Islet Cell Hormonal Responses to Hypoglycemia After Human Islet Transplantation for Type 1 Diabetes

Abstract

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. Diabetes 54: 3205-3211, 2005

Islet cell transplantation today

“…They clearly demonstrated that islet transplantation provides endogenous insulin that corrects glycemic lability and is accompanied by a decrease in the number of episodes of hypoglycemia [44]. However, our earlier findings of a lack of islet transplantation on the blunted glucagon response to hypoglycemia was recently confirmed [45]. Nonetheless, the beneficial effects on glucose stability and hypoglycemia awareness have to be ascribed to successful islet transplantation.…”

Positron Emission Tomography in Clinical Islet Transplantation

“…The radioactivity uptake peak in the liver represented 62.9 (53. 4 Figure 4 (range not shown) The flowchart in Figure 5 shows how the administered islets distribute in the liver lobes and main segments, respectively. The (6,(25)(26)(27)(28)(29)(30) (10).…”

Glucose-responsive beta cells in islets isolated from a patient with long-standing type 1 diabetes mellitus

“…In addition, it demonstrates that the residual beta cells remain responsive to glucose, although the abundant alpha cells were not responsive to changes in glucose concentration. The observed impaired response of the alpha cells may contribute to the counterregulatory dysfunction known to occur in these patients [10].…”