TY - JOUR
T1 - Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake
AU - Schutten, Monica T. J.
AU - Kusters, Yvo H. A. M.
AU - Houben, Alfons J. H. M.
AU - Niessen, Hanneke E.
AU - Roodt, Jos Op't
AU - Scheijen, Jean L. J. M.
AU - van de Waardenburg, Marjo P.
AU - Schalkwijk, Casper G.
AU - de Leeuw, Peter W.
AU - Stehouwer, Coen D. A.
N1 - Funding Information:
We thank the dieticians of the Maastricht University Medical Center for the dietary counseling of the participants in this trial and V. Vermeulen (Department of Internal Medicine, Maastricht University Medical Center) for assistance during the execution of this study.
Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.
PY - 2020/3/26
Y1 - 2020/3/26
N2 - BACKGROUND. Salt-sensitive hypertension is often accompanied by insulin resistance in obese individuals, but the underlying mechanisms are obscure. Microvascular function is known to affect both salt sensitivity of blood pressure and metabolic insulin sensitivity. We hypothesized that excessive salt intake increases blood pressure and decreases insulin-mediated glucose disposal, at least in part by impairing insulin-mediated muscle microvascular recruitment (IMMR).METHODS. In 20 lean and 20 abdominally obese individuals, we assessed mean arterial pressure (MAP; 24-hour ambulatory blood pressure measurements), insulin-mediated whole-body glucose disposal (M/I value; hyperinsulinemic-euglycemic clamp technique), IMMR (contrast-enhanced ultrasound), osmolyte and water balance, and excretion of mineralocorticoids, glucocorticoids, and amino and organic acids after a low- and high-salt diet during 7 days in a randomized, double-blind, crossover design.RESULTS. On a low-, as compared with a high-salt, intake, MAP was lower, M/I value was lower, and IMMR was greater in both lean and abdominally obese individuals. In addition, natural logarithm IMMR was inversely associated with MAP in lean participants on a low-salt diet only. On a high-salt diet, free water clearance decreased, and excretion of glucocorticoids and of amino acids involved in the urea cycle increased.CONCLUSION. Our findings imply that hemodynamic and metabolic changes resulting from alterations in salt intake are not necessarily associated. Moreover, they are consistent with the concept that a high-salt intake increases muscle glucose uptake as a response to high salt-induced, glucocorticoid-driven muscle catabolism to stimulate urea production and thereby renal water conservation.
AB - BACKGROUND. Salt-sensitive hypertension is often accompanied by insulin resistance in obese individuals, but the underlying mechanisms are obscure. Microvascular function is known to affect both salt sensitivity of blood pressure and metabolic insulin sensitivity. We hypothesized that excessive salt intake increases blood pressure and decreases insulin-mediated glucose disposal, at least in part by impairing insulin-mediated muscle microvascular recruitment (IMMR).METHODS. In 20 lean and 20 abdominally obese individuals, we assessed mean arterial pressure (MAP; 24-hour ambulatory blood pressure measurements), insulin-mediated whole-body glucose disposal (M/I value; hyperinsulinemic-euglycemic clamp technique), IMMR (contrast-enhanced ultrasound), osmolyte and water balance, and excretion of mineralocorticoids, glucocorticoids, and amino and organic acids after a low- and high-salt diet during 7 days in a randomized, double-blind, crossover design.RESULTS. On a low-, as compared with a high-salt, intake, MAP was lower, M/I value was lower, and IMMR was greater in both lean and abdominally obese individuals. In addition, natural logarithm IMMR was inversely associated with MAP in lean participants on a low-salt diet only. On a high-salt diet, free water clearance decreased, and excretion of glucocorticoids and of amino acids involved in the urea cycle increased.CONCLUSION. Our findings imply that hemodynamic and metabolic changes resulting from alterations in salt intake are not necessarily associated. Moreover, they are consistent with the concept that a high-salt intake increases muscle glucose uptake as a response to high salt-induced, glucocorticoid-driven muscle catabolism to stimulate urea production and thereby renal water conservation.
KW - DIETARY-SODIUM RESTRICTION
KW - BLOOD-PRESSURE
KW - SKELETAL-MUSCLE
KW - INBORN-ERRORS
KW - UREA CYCLE
KW - RESISTANCE
KW - OBESITY
KW - REDUCTION
KW - AICAR
KW - RATS
U2 - 10.1172/jci.insight.127530
DO - 10.1172/jci.insight.127530
M3 - Article
C2 - 32107343
SN - 2379-3708
VL - 5
JO - JCI INSIGHT
JF - JCI INSIGHT
IS - 6
M1 - 127530
ER -