4.7 Article

Insulin-mediated muscle microvascular perfusion and its phenotypic predictors in humans

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SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

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NATURE RESEARCH
DOI: 10.1038/s41598-021-90935-8

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  1. National Institutes of Health [R01DK102359, R01DK125330, R01DK124344, F32 DK121431]
  2. National Center for Advancing Translational Sciences of the National Institutes of Health [KL2TR003016/ULTR003015]

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This study found that muscle microvascular insulin responses were mainly predicted by M-value and VO(2)max, while predictors of metabolic insulin resistance did not significantly predict microvascular insulin responses.
Insulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications. Insulin-mediated whole-body glucose disposal rates (M-value) and insulin-induced changes in muscle microvascular blood volume (Delta MBV) were determined. Univariate and multivariate analyses were conducted to examine bivariate and multivariate relationships between outcomes, Delta MBV and M-value, and predictor variables, body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximum consumption of oxygen (VO(2)max), plasma LDL (LDL-C) and HDL cholesterol, triglycerides (TG), and fasting insulin (INS) levels. Among all factors, only M-value (r=0.23, p=0.02) and VO(2)max (r=0.20, p=0.047) correlated with Delta MBV. Conversely, INS (r=- 0.48, p <= 0.0001), BF (r=- 0.54, p <= 0.001), VO(2)max (r=0.5, p <= 0.001), BMI (r=- 0.40, p<0.001), WT (r=- 0.33, p=0.001), LDL-C (r=- 0.26, p=0.009), TG (r=- 0.25, p=0.012) correlated with M-value. While both MBV (p=0.045) and TG (p=0.03) provided significant predictive information about M-value in the multivariate regression model, only M-value was uniquely predictive of Delta MBV (p=0.045). Thus, both M-value and VO(2)max correlated with Delta MBV but only M-value provided unique predictive information about Delta MBV. This suggests that metabolic and microvascular insulin responses are important predictors of one another, but most metabolic insulin resistance predictors do not predict microvascular insulin responses.

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