To determine the effect of sympathetic neural and hormonal (epinephrine) input on islet cell
hormonal responses to insulin-induced hypoglycemia in type 1 diabetic recipients of
intrahepatic islet transplantation. We hypothesize that α-adrenergic (neural) blockage will
abolish insulin-mediated suppression of C-peptide, attenuating α-cell glucagon secretion
during hypoglycemia, and that β-adrenergic (hormonal) blockage will have no effect. Glucose
counterregulatory responses will be measured during hyperinsulinemic euglycemic-hypoglycemic
clamps on three occasions with randomized, double-blind administration of the α-adrenergic
blocker phentolamine, the β-adrenergic blocker propranolol, or placebo. The demonstration of
neural rather than hormonal regulation of the transplanted islet cell response to
hypoglycemia is critical for understanding the mechanism for protection from hypoglycemia
afforded by intrahepatically transplanted.
Phase:
Early Phase 1
Details
Lead Sponsor:
University of Pennsylvania
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) National Institutes of Health (NIH)