Twenty-eight-day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides

Abstract

Spaceflight represents a unique physiologic challenge to humans, altering hormonal profiles and tissue insulin sensitivity. Among these hormonal alterations, hypercortisolemia and insulin insensitivity are thought to negatively affect muscle mass and function with spaceflight. As insulin sensitivity influences the accumulation of muscle triglycerides, we examined this relationship during hypercortisolemia and inactivity. Six young healthy volunteers were confined to bed rest for 28 days. To mimic the stress response observed during spaceflight, hypercortisolemia (20-24 mg/dL) was induced and maintained by oral ingestion of hydrocortisone. On days 1 and 28 of bed rest, insulin sensitivity across the leg was assessed with a local (femoral arterial insulin infusion) 2-stage hyperinsulinemic-euglycemic clamp (stage 1, 35 microU/min per milliliter of leg; stage 2, 70 microU/min per milliliter of leg). Intramuscular lipid was measured with magnetic resonance spectroscopy. After bed rest, there was a decrease in insulin sensitivity, as assessed by glucose uptake during hyperinsulinemia (from 9.1 +/- 1.3 [mean +/- SEM] to 5.2 +/- 0.7 mg/kg of leg per minute [P = .015]). Intramuscular triglyceride increased from 0.077 +/- 0.011 to 0.136 +/- 0.018 (signal area of fat/signal area of standard, P = .009). Intramuscular lipid content correlated with the glucose uptake at day 28 (R = -0.85, P = .035). These data demonstrate that muscular inactivity and hypercortisolemia are associated with an increase in intramuscular triglyceride and skeletal muscle insulin resistance in previously healthy subjects.

Conflict of interest statement

No author claims a conflict of interest

Figures

Figure 1

Experimental and pre- and post- bed rest infusion protocol (expanded).

Figure 2

Individual subject values of leg glucose uptake (A) and intramuscular triglycerides (IMTG; B). A) leg glucose uptake (as assessed by glucose infusion rate to maintain euglycemia) before and after bed rest in each individual patient. Uptake decreases significantly following bed rest; (P=0.015). B) IMTG in each individual patient before and after bed rest. IMTG increased in each subject and was significant for the group; P=0.009

Figure 3

IMTG and glucose clamp correlations post bed rest. Leg glucose uptake (mg/kg/min) and IMTG (AU; pt value compared to standard) were significantly related following 28 days of hypercortisolemic bed rest with a R= −0.85; (P=0.035).

Figure 4

Femoral vein plasma non-esterified free fatty acid (NEFA) and glycerol concentrations in response to 2 levels of intra-arterial insulin infusion. A) Plasma NEFA concentrations decreased in response to insulin equally before and after bed rest. B) Plasma glycerol decreased in response to insulin equally before and after bed rest. +; p =0.003 pre vs post at the high insulin level. *; p=0.01 high insulin vs basal, pre and post bed rest.

Figure 5

Intramuscular diacylglycerol palmitoyl concentrations. Concentrations did not change with exposure to insulin, or following bed rest.