Journal
DIABETES
Volume 53, Issue 8, Pages 2051-2059Publisher
AMER DIABETES ASSOC
DOI: 10.2337/diabetes.53.8.2051
Keywords
-
Categories
Funding
- NCRR NIH HHS [RR-00585] Funding Source: Medline
- NIDDK NIH HHS [DK29953] Funding Source: Medline
Ask authors/readers for more resources
Glucocorticoids are potent regulators of protein, fat, and carbohydrate metabolism. To determine if cortisol production occurs within the splanchnic bed in humans, 11 nondiabetic subjects were studied using the hepatic/leg catheterization method along with an infusion of [9,11,12,12-H-2(4)] cortisol (D4-cortisol) as proposed by Andrews et al. In the fasting state, there was net release (P < 0.05) of cortisol from the splanchnic bed (6.1 +/- 2.6 g/min) and net uptake (P < 0.05) by the leg (1.7 +/- 0.7 mug/min). This, along with cortisol production by other tissues (e.g., the adrenals), resulted in a total-body ortisol appearance rate of 18.1 +/- 1.9 mug/min. Fractional splanchnic D4-cortisol extraction averaged 12.9 +/- 1.3% (P < 0.001), splanchnic cortisol uptake 14.8 +/- 2.0 mug/min (P < 0.001), and splanchnic cortisol production 22.2 +/- 3.3 mug/min (P < 0.001). On the other hand, fractional leg D4-cortisol extraction averaged 5.6 +/- 1.8% (P < 0.02), leg cortisol uptake 2.3 +/- 0.7 mug/min (P < 0.01), and leg cortisol production 0.4 +/- 0.4 mug/min, which did not differ from zero. Because D4-cortisol loses a deuterium during conversion to [9,12,12-H-2(3)] cortisone (D3-cortisone), which in turn generates [9,12,12(2)H(3)] cortisol (D3-cortisol) via 11-beta hydroxysteroid dehydrogenase (11beta-HSD) type 1, D3-cortisol production can be used as an index of 11beta-HSD type 1 activity. Net splanchnic D3-cortisol release (3.9 +/- 0.4 mug/min) and splanchnic D3-cortisol production (7.1 +/- 0.7 mug/min) occurred (P < 0.01) in all subjects. In contrast, there was minimal leg D3-cortisol production (0.04 +/- 0.01 mug/min), resulting in a strong correlation between splanchnic D3-cortisol production and total-body 3D-cortisol production in both the fasting state (r = 0.84; P < 0.02) and during an infusion of insulin (r = 0.97; P < 0.01). Thus, splanchnic production of cortisol occurs in nondiabetic humans at rates approximating that which occurs in the remainder of the body. These data support the possibility that alterations in splanchnic cortisol production contribute to visceral fat accumulation and the hepatic insulin resistance of obesity or type 2 diabetes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available