Influence of circulating epinephrine on absorption of subcutaneously injected insulin

Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol.kg-1.min-1 i.v., resulting in arterial plasma Epi levels of approximately 6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased approximately 40-50% during the high dose of Epi compared with control (P less than .001). The corresponding decrease from the abdominal depot was approximately 40% (P less than .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin.