Insulin increases ventilation during euglycemia in humans

Evidence from animal studies indicates that hyperinsulinemia, without changes in glucose, increases ventilation via a carotid body-mediated mechanism. However, whether insulin elevates ventilation in humans independently of changes in glucose remains unclear. Therefore, we tested the hypothesis that insulin increases ventilation in humans during a hyperinsulinemic-euglycemic clamp in which insulin was elevated to postprandial concentrations while glucose was maintained at fasting concentrations. First, in 16 healthy young men (protocol 1), we retrospectively analyzed respiration rate and estimated tidal volume from a pneumobelt to calculate minute ventilation during a hyperinsulinemic-euglycemic clamp. In addition, for a direct assessment of minute ventilation during a hyperinsulinemic-euglycemic clamp, we retrospectively analyzed breath-by-breath respiration rate and tidal volume from inspired/expired gasses in an additional 23 healthy young subjects (protocol 2). Clamp infusion elevated minute ventilation from baseline in both protocols (protocol 1: =11.9-4.6% baseline, P < 0.001; protocol 2: =9.5-3.8% baseline, P < 0.020). In protocol 1, peak changes in both respiration rate (=13.9-3.0% baseline, P < 0.001) and estimated tidal volume (=16.9-4.1% baseline, P < 0.001) were higher than baseline during the clamp. In protocol 2, tidal volume primarily increased during the clamp (=9.7-3.7% baseline, P < 0.016), as respiration rate did not change significantly (=0.2-1.8% baseline, P < 0.889). Collectively, we demonstrate for the first time in humans that elevated plasma insulin increases minute ventilation independent of changes in glucose.