Citations

The splanchnic bed produces cortisol at rates approximating extraadrenal tissues by converting cortisone to cortisol via the 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 pathway. It is not known whether splanchnic cortisol production is regulated by nutrient ingestion and/or by the accompanying changes in hormone secretion. To address this question, 18 healthy humans were randomized to ingest either a mixed meal or to receive an intravenous saline infusion while total-body, splanchnic, and d3 cortisol production (an index of 11β-HSD type 1 activity) were measured using the combined hepatic catheterization and d4 cortisol infusion methods. Fasting glucose and insulin concentrations did not differ on the meal and saline study days. Glucose and insulin concentrations increased after meal ingestion, peaking at 11.0 ± 1.0 mmol/l and 451 ± 64 pmol/l, respectively, at 45 min, then fell to baseline thereafter. In contrast, glucose and insulin concentrations slowly fell to 5.1 ± 0.1 mmol/l and 27 ± 6 pmol/l during the 6 h of observation on the saline study day. Fasting cortisol concentration did not differ on the meal and saline study days. Cortisol increased (P < 0.05) to a peak of 353 ± 55 nmol/l after meal ingestion but did not change after saline infusion. The increase in cortisol after meal ingestion was associated with an increase in both total body cortisol (from 748 ± 63 to 1,620 ± 235 nmol/min; P < 0.01) and total body d3 cortisol (from 99 ± 11 to 143 ± 11 nmol/min; P < 0.01) production, whereas there was no change in either on the saline study day. The increase in total-body cortisol and d3 cortisol production after meal ingestion originated in extrasplanchnic tissues since splanchnic cortisol production (mean 0–360 min: 254 ± 83 vs. 262 ± 36 nmol/min) and splanchnic d3 cortisol production (mean 0–360 min: 72 ± 22 vs. 77 ± 14 nmol/min) did not differ on the meal and saline study days. We conclude that ingestion of a mixed meal does not alter either splanchnic cortisol production or the conversion of d4 cortisol to d3 cortisol or, therefore by implication, flux via the splanchnic 11β-HSD type 1 pathway.

Abstract Context: Cortisol is a potent regulator of carbohydrate, fat, and protein metabolism. Objective: The objective of the study was to determine whether obesity alone or in combination with type 2 diabetes increases splanchnic and/or leg cortisol production. Design: Splanchnic and leg cortisol production were measured using the hepatic and leg catheterization technique combined with infusion of D4-cortisol. Setting: The study was conducted in a General Clinical Research Center. Participants: Nine lean nondiabetic, 10 obese nondiabetic, and 11 obese diabetic subjects were studied. Interventions: Diabetic volunteers were withdrawn from their glucose-lowering medications before study. Main Outcome Measures: Rates of total body, splanchnic and leg cortisol, and D3-cortisol production were measured. Results: Rates of splanchnic cortisol production equaled or exceeded those occurring in extrasplanchnic tissues (e.g. the adrenals) in all three groups. However, because concurrent splanchnic cortisol uptake also occurred, net splanchnic cortisol release was minimal. Splanchnic cortisol production and splanchnic D3-cortisol production (an index of splanchnic 11β-hydroxysteroid dehydrogenase type 1 activity) did not differ among the three groups. In addition, splanchnic cortisol production did not correlate with either visceral fat or endogenous glucose production. On the other hand, splanchnic cortisol uptake was greater in the obese diabetic than lean nondiabetic subjects (25 ± 2.9 vs. 15.3 ± 2.5 μg/min; P < 0.05). Splanchnic, but not leg, D3-cortisol production was correlated with total body D3-cortisol production (r = 0.70; P < 0.001). Conclusions: Although large amounts of cortisol are produced within the splanchnic bed, implying high intrahepatic glucocorticoid concentrations, rates do not differ in lean and obese nondiabetic humans and are not influenced by the presence of type 2 diabetes mellitus. On the other hand, obesity but not diabetes increases splanchnic cortisol uptake.