359-OR: a- or ß-Adrenergic Blockade Does Not Affect Transplanted Islet Responses to Hypoglycemia in Type 1 Diabetes (T1D)

Recipients of intrahepatic islet transplantation for T1D exhibit appropriate suppression of endogenous insulin and activation of glucagon secretion in response to insulin-induced hypoglycemia with restored glucose counterregulation and protection against clinically significant hypoglycemia. Whether sympathetic activation of adrenergic receptors on transplanted islets is required for these responses is not known. To evaluate the adrenergic contribution to post-transplant glucose counterregulation, we performed a randomized, double-blind crossover study of responses during a hyperinsulinemic (1 mU·kg-1·min-1) euglycemic (EU, ∼90 mg/dL)-hypoglycemic (HYPO, ∼50 mg/dL) clamp conducted under phentolamine (0.95 µg·kg-1·min-1; α-adrenergic blockage), propranolol (0.48 µg·kg-1·min-1; β-adrenergic blockage), or placebo infusion. Subjects were 5F/4M with median (range) age 53 (34 - 63) years, T1D duration 29 (18 - 56) years, post-transplant 7 (2 - 8) years, HbA1c 5.8 (4.5 - 6.8) %, insulin in-/dependent 5/4, on tacrolimus-based immunosuppression, and spent 97 (76 - 99) % time in range 70 - 180 mg/dL and 1 (0 - 3) % time with hypoglycemia Disclosure M.R. Rickels: Consultant; Self; Semma Therapeutics, Inc. Research Support; Self; Xeris Pharmaceuticals, Inc. M. Bellin: Research Support; Self; Dexcom, Inc., Viacyte, Inc. Other Relationship; Self; Insulet Corporation. D. Stefanovski: None. A.J. Peleckis: None. C.V. Dalton-Bakes: None. E. Markmann: None. H.T. Nguyen: None. A. Naji: None. Funding National Institutes of Health (R01DK091331, UL1TR001878, P30DK19525)