Low‐dose Dopamine, but Not Acute Hyperoxia, Attenuates the Sympathoexcitatory Response to Hyperinsulinemia in Healthy Humans
Authors: Limberg Jacqueline K , Mozer Michael T , Holbein Walter W , Johnson Blair D , Prabhakar Nanduri R , Curry Timothy B , Joyner Michael J 
Published: November 2023

ObjectiveInsulin has known sympathoexcitatory effects that have been historically attributed to primarily central mechanisms. Although controversy exists, recent evidence from rodents suggests the carotid chemoreceptors may play a role in the sympathoexcitatory response to hyperinsulinemia. Therefore, we sought to examine the contribution of the carotid chemoreceptors to insulin‐mediated increases in sympathetic nervous system activity in humans. We hypothesized reductions in carotid chemoreceptor activity would attenuate the sympathoexcitatory response to hyperinsulinemia in humans – thus supporting a role for the carotid chemoreceptors in insulin‐mediated sympathoexcitation.MethodsYoung, healthy adults (n=15, 8M/7F, 27±1 yrs, 24±1 kg/m2) completed a 30‐min euglycemic baseline followed by a 90‐min hyperinsulinemic (1 mU/kg FFM/min), euglycemic (90–100 mg/dL) clamp. Heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA, microneurography of the peroneal nerve) were continuously measured. The role of the carotid chemoreceptors was assessed using the following protocols: 1) acute (1‐min) hyperoxia (n=13), 2) low‐dose dopamine (1–4 μg/kg/min; n=7), 3) acute hyperoxia + low‐dose dopamine (n=8). The nadir 15‐s value for MSNA within each hyperoxic condition was determined and the nadir at baseline was compared to the nadir during hyperinsulinemia.ResultsMSNA increased from baseline during the hyperinsulinemic, euglycemic clamp [12±2 to 18±2 bursts/min (p<0.01)]. In protocol 1, MSNA was reduced during acute hyperoxia at baseline (12±1 to 6±1 bursts/min, p<0.01) and during the hyperinsulinemic clamp (17±2 to 12±2 bursts/min, p=0.02); however, the fall in MSNA during hyperoxia did not differ between baseline and hyperinsulinemia (p=0.82). In protocol 2, when low‐dose dopamine was given prior to the hyperinsulinemic clamp, MSNA did not increase from baseline (19±2 to 22±5 bursts/min, p=0.51); this is in contrast to increases observed under saline conditions (14±3 to 22±4 bursts/min, p=0.03). In protocol 3, in the presence of low‐dose dopamine, MSNA was reduced during acute hyperoxia at baseline (16±3 to 9±2 bursts/min, p=0.048) and during the hyperinsulinemic clamp (16±4 to 9±3 bursts/min, p=0.02); however, the fall in MSNA with hyperoxia did not differ between baseline and hyperinsulinemia (p=0.97).ConclusionsLow‐dose dopamine given prior to the onset of a hyperinsulinemic, euglycemic clamp attenuates the sympathoexcitatory response to hyperinsulinemia. In contrast, acute carotid chemoreceptor desensitization (1‐min hyperoxia) during steady‐state hyperinsulinemia does not augment the fall in MSNA observed at baseline. Our data suggest the carotid chemoreceptors do not contribute acutely to insulin‐mediated increases in sympathetic nervous system activity in healthy humans; however, they may play a role during longer‐term exposure.Support or Funding InformationSupport: DK090541 (MJJ); HL83947 (MJJ); HL130339 (JKL); AHA15SDG25080095 (JKL)