Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis

J. J. Winnick, C. J. Ramnanan, Saraswathi Viswanathan, J. Roop, M. Scott, P. Jacobson, P. Jung, R. Basu, A. D. Cherrington, D. S. Edgerton

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The aim of this study was to determine the effect of prolonged 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibition on basal and hormone-stimulated glucose metabolism in fasted conscious dogs. For 7 days prior to study, either an 11β-HSD1 inhibitor (HSD1-I; n = 6) or placebo (PBO; n = 6) was administered. After the basal period, a 4-h metabolic challenge followed, where glucagon (3×-basal), epinephrine (5×-basal), and insulin (2×-basal) concentrations were increased. Hepatic glucose fluxes did not differ between groups during the basal period. In response to the metabolic challenge, hepatic glucose production was stimulated in PBO, resulting in hyperglycemia such that exogenous glucose was required in HSD-I (P < 0.05) to match the glycemia between groups. Net hepatic glucose output and endogenous glucose production were decreased by 11β-HSD1 inhibition (P < 0.05) due to a reduction in net hepatic glycogenolysis (P < 0.05), with no effect on gluconeogenic flux compared with PBO. In addition, glucose utilization (P < 0.05) and the suppression of lipolysis were increased (P < 0.05) in HSD-I compared with PBO. These data suggest that inhibition of 11β-HSD1 may be of therapeutic value in the treatment of diseases characterized by insulin resistance and excessive hepatic glucose production.

Original languageEnglish (US)
Pages (from-to)E747-E756
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume304
Issue number7
DOIs
StatePublished - Apr 1 2013

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11-beta-Hydroxysteroid Dehydrogenases
Glycogenolysis
Gluconeogenesis
Glucose
Liver
Lipolysis
Glucagon
Hyperglycemia
Epinephrine
Insulin Resistance
Placebos
Hormones
Dogs
Insulin

Keywords

  • 11ß-hydroxysteroid dehydrogenase-1
  • Cortisol
  • Gluconeogenesis
  • Glycogenolysis
  • Hepatic glucose production

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis. / Winnick, J. J.; Ramnanan, C. J.; Viswanathan, Saraswathi; Roop, J.; Scott, M.; Jacobson, P.; Jung, P.; Basu, R.; Cherrington, A. D.; Edgerton, D. S.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 304, No. 7, 01.04.2013, p. E747-E756.

Research output: Contribution to journalArticle

Winnick, JJ, Ramnanan, CJ, Viswanathan, S, Roop, J, Scott, M, Jacobson, P, Jung, P, Basu, R, Cherrington, AD & Edgerton, DS 2013, 'Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis', American Journal of Physiology - Endocrinology and Metabolism, vol. 304, no. 7, pp. E747-E756. https://doi.org/10.1152/ajpendo.00639.2012
Winnick, J. J. ; Ramnanan, C. J. ; Viswanathan, Saraswathi ; Roop, J. ; Scott, M. ; Jacobson, P. ; Jung, P. ; Basu, R. ; Cherrington, A. D. ; Edgerton, D. S. / Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis. In: American Journal of Physiology - Endocrinology and Metabolism. 2013 ; Vol. 304, No. 7. pp. E747-E756.
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AU - Scott, M.

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