Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

Journal Article · Thu Nov 01 04:00:00 EST 1990 · American Journal of Physiology; (USA)

OSTI ID:6274995

Wajngot, A; Khan, A; Giacca, A; Vranic, M; Efendic, S ^[1]

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1. Karolinska Hospital, Stockholm (Sweden)

We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with (2-3H)glucose and HGP with (6-3H)glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). (2-3H)- minus (6-3H)glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

• OSTI ID: 6274995
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 259:5 Pt 1; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALDEHYDES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
CARBOHYDRATES
CORTICOSTEROIDS
DEXAMETHASONE
DIGESTIVE SYSTEM
GLANDS
GLUCOCORTICOIDS
GLUCOSE
HEXOSES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
LIVER
MAMMALS
MAN
METABOLISM
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANS
PREGNANES
PRIMATES
REACTION KINETICS
SACCHARIDES
STEROIDS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES