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Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake.

ABSTRACT: BACKGROUNDSalt-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).METHODSIn 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.RESULTSOn 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.CONCLUSIONOur 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.TRIAL REGISTRATIONClinicalTrials.gov, NCT02068781.

SUBMITTER: Schutten MT

PROVIDER: S-EPMC7213801 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake.

Schütten Monica Tj MT Kusters Yvo Ham YH Houben Alfons Jhm AJ Niessen Hanneke E HE Op 't Roodt Jos J Scheijen Jean Ljm JL van de Waardenburg Marjo P MP Schalkwijk Casper G CG de Leeuw Peter W PW Stehouwer Coen DA CD

JCI insight 20200326 6

BACKGROUNDSalt-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).METHODSIn 20 lean and 20 abdomina ...[more]

PMID: 32107343

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Project description:AimsAngiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin's microvascular and metabolic actions in skeletal muscle.Methods and resultsAdult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinaemic euglycaemic clamp), or insulin (hyperinsulinaemic euglycaemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinaemic euglycaemic clamp) infusion. In all animals' systemic metabolic effects, central haemodynamics, femoral artery blood flow, microvascular blood flow, and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate, and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinaemic euglycaemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin's effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate, or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow, and this was accompanied by reduced skeletal muscle glucose uptake.ConclusionsAcute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin's microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.

Project description:PURPOSE:Bariatric surgery is considered as an effective therapeutic strategy for weight loss in severe obesity. Remission of type 2 diabetes is often achieved after the surgery. We investigated whether increase in self-reported habitual physical activity associates with improved skeletal muscle insulin sensitivity and reduction of fat depots after bariatric surgery. METHODS:We assessed self-reported habitual physical activity using Baecke questionnaire in 18 diabetic and 28 nondiabetic patients with morbid obesity (median age, 46 yr; body mass index, 42.0 kg·m) before and 6 months after bariatric surgery operation. Insulin-stimulated femoral muscle glucose uptake was measured using fluorodeoxyglucose positron emission tomography method during hyperinsulinemia. In addition, abdominal subcutaneous and visceral fat masses were quantified using magnetic resonance imaging and liver fat content using magnetic resonance spectroscopy. Also, serum proinflammatory cytokines were measured. RESULTS:Patients lost on average 22.9% of weight during the follow-up period of 6 months (P < 0.001). Self-reported habitual physical activity level increased (P = 0.017). Improvement in skeletal muscle insulin sensitivity was observed only in those patients who reported increase in their physical activity postoperatively (P = 0.018). The increase in self-reported physical activity associated with the loss of visceral fat mass (P = 0.029). Postoperative self-reported physical activity correlated also positively with postoperative hepatic insulin clearance (P = 0.02) and tended to correlate negatively with liver fat content (P = 0.076). Postoperative self-reported physical activity also correlated negatively with serum TNF?, methyl-accepting chemotaxis protein and interleukin 6 levels. CONCLUSIONS:Self-reported physical activity is associated with reversal of skeletal muscle insulin resistance after bariatric surgery as well as with the loss of visceral fat content and improved postoperative metabolism in bariatric surgery patients. TRIAL REGISTRATION:Clinicaltrials.gov, NCT00793143 (SLEEVEPASS), NCT01373892 (SLEEVEPET2).

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Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake.

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Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake.

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