The effect of norepinephrine on insulin secretion and glucose effectiveness in non-insulin-dependent diabetes

It has previously been shown that in normal subjects, physiological elevation of norepinephrine (NE) impairs insulin sensitivity (Si) but does not influence insulin secretion. The aim of this study was to determine the effect of short-term physiological elevation of NE on insulin secretion, Si, and glucose-mediated glucose disposal, or the glucose effectiveness index (Sg), in non-insulin-dependent diabetes mellitus (NIDDM). Two intravenous glucose tolerance tests (IVGTTs) were performed in eight well-controlled NIDDM patients, using a supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. The IVGTTs were performed in random order after 30 minutes of either the saline (SAL) or NE (25 ng/kg/min) infusions, which were continued throughout the 3-hour IVGTT. Sg and Si were estimated by minimal model analysis of the IVGTT data as previously described. Plasma C-peptide was used to estimate insulin secretion rate using the ISEC program. NE infusion produced approximately a threefold increase in plasma NE, associated with (1) a significant reduction in glucose disposal ([K_G] SAL v NE, 0.73 ± 0.06 v 0.61 ± 0.06 × 10⁻² · min⁻², P < .05), (2) no reduction in Si (2.33 ± 0.8 v 2.62 ± 0.9 × 10⁻⁴ · min⁻¹/mU/L, NS), (3) a reduced mean second-phase insulin secretion rate (1.21 ± 0.19 v 1.01 ± 0.16 × 10⁻³ pmol/kg/min per mmol/L glucose, P < .05), (4) a significant increase in Sg (0.89 ± 0.08 v 1.63 ± 0.2 × 10⁻² · min⁻¹ P < .05), and (5) a corresponding increase in glucose effectiveness at zero insulin ([GEZI] 0.55 ± 0.13 v 1.30 ± 0.33 × 10⁻² · min⁻¹, P < .05). These results show that in contrast to normal subjects, physiological elevation of NE in NIDDM does not result in a reduction in Si, but causes a reduction in glucose disposal related to inhibition of insulin secretion that is only partially compensated for by increased Sg.