Functional adaptation of the human β-cells after frequent exposure to noradrenaline

Abstract

Key points: Trained people produce less insulin than untrained; there is an adaptation of the insulin-producing cells to the trained state. The mechanism behind this adaptation is not known, but some sort of memory must be introduced into the insulin-producing cells. Here it is shown that this memory is introduced by 10 daily intravenous infusions of noradrenaline, mimicking the increases that occur during a 10 day training programme. Thus, after the infusion period, the subjects produced less insulin in response to the same stimulus. It is concluded that exercise-induced increases in noradrenaline is most likely the stimulus that introduces a memory in the insulin-producing cells. Physical training decreases glucose- and arginine-stimulated insulin secretion. The mechanism by which the pancreatic β-cells adapt to the training status of the individual is not known. We hypothesized that the adaptation is mediated via the frequent exercise-induced increases in sympathetic activity. Simulation of exercise-induced increases in plasma noradrenaline (NA) concentrations was carried out in nine untrained men (age: 25 ± 1 years (mean ± SEM); BMI: 24 ± 1 kg m-2), who received infusions of NA (0.2 μg kg-1 min-1) for 45 min every day for 10 days. The insulin response to glucose was measured during hyperglycaemic (20 mmol l-1) clampsbefore and after the NA infusion period. During NA infusions mean arterial blood pressure increased (from 89 ± 2 to 110 ± 5 mmHg, P < 0.05) and heart rate decreased (from 78 ± 7 to 69 ± 12 beats min-1, P < 0.05). During NA infusions plasma insulin concentrations decreased to nadir by 68% (P < 0.05). Fasting plasma glucose and insulin were not different at the two clamps (5.3 ± 0.1 and 5.3 ± 0.3 mmol l-1; 47 ± 15 and 31 ± 4 pmol l-1, respectively). Plasma glucose concentrations during the hyperglycaemic clamps were similar (P > 0.05) and averaged 19.9 ± 0.1 mmol l-1 with a coefficient of variation of 3.8 ± 0.3%, while the insulin response decreased (P < 0.05) by 26 ± 2% after the 10 days of NA infusions. It is concluded that NA mediates the adaptation of the β-cells seen in trained people.