PMID- 22321826
OWN - NLM
STAT- MEDLINE
DCOM- 20130418
LR  - 20220317
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 14
IP  - 10
DP  - 2012 Oct
TI  - 11beta-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the 
      pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus.
PG  - 869-81
LID - 10.1111/j.1463-1326.2012.01582.x [doi]
AB  - Recent evidence strongly argues for a pathogenic role of glucocorticoids and 
      11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in obesity and the metabolic 
      syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease 
      and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), 
      dyslipidaemia, hypertension and visceral obesity. This has been partially 
      prompted not only by the striking clinical resemblances between the metabolic 
      syndrome and Cushing's syndrome (a state characterized by hypercortisolism that 
      associates with metabolic syndrome components) but also from monogenic rodent 
      models for the metabolic syndrome (e.g. the leptin-deficient ob/ob mouse or the 
      leptin-resistant Zucker rat) that display overall increased secretion of 
      glucocorticoids. However, systemic circulating glucocorticoids are not elevated 
      in obese patients and/or patients with metabolic syndrome. The study of the role 
      of 11beta-HSD system shed light on this conundrum, showing that local 
      glucocorticoids are finely regulated in a tissue-specific manner at the 
      pre-receptor level. The system comprises two microsomal enzymes that either 
      activate cortisone to cortisol (11beta-HSD1) or inactivate cortisol to cortisone 
      (11beta-HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 
      or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, 
      have been developed and helped unravel the currently undisputable role of the 
      enzymes in metabolic syndrome pathophysiology, in each of its isolated components 
      and in their prevention. In the transgenic HSD11B1 overexpressing models, 
      different features of the metabolic syndrome and obesity are replicated. HSD11B1 
      gene deficiency or HSD11B2 gene overexpression associates with improvements in 
      the metabolic profile. In face of these demonstrations, research efforts are now 
      being turned both into the inhibition of 11beta-HSD1 as a possible pharmacological 
      target and into the role of dietary habits on the establishment or the prevention 
      of the metabolic syndrome, obesity and T2DM through 11beta-HSD1 modulation. We 
      intend to review and discuss 11beta-HSD1 and obesity, the metabolic syndrome and 
      T2DM and to highlight the potential of its inhibition for therapeutic or 
      prophylactic approaches in those metabolic diseases.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Pereira, C D
AU  - Pereira CD
AD  - Department of Biochemistry (U38/FCT), Faculty of Medicine, University of Porto, 
      Portugal.
FAU - Azevedo, I
AU  - Azevedo I
FAU - Monteiro, R
AU  - Monteiro R
FAU - Martins, M J
AU  - Martins MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120308
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Glucocorticoids)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 1)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & 
      inhibitors/*pharmacology
MH  - Adipose Tissue/enzymology
MH  - Animals
MH  - Anti-Inflammatory Agents
MH  - Atherosclerosis/drug therapy/*enzymology
MH  - Corticosterone/blood
MH  - Cushing Syndrome/diagnosis/diet therapy/*enzymology
MH  - Diabetes Mellitus, Type 2/drug therapy/*enzymology
MH  - Female
MH  - Glucocorticoids/*blood
MH  - Humans
MH  - Liver/enzymology
MH  - Male
MH  - Metabolic Syndrome/diagnosis/drug therapy/*enzymology
MH  - Mice
MH  - Mice, Transgenic
MH  - Obesity/drug therapy/*enzymology
MH  - Rats
MH  - Rats, Transgenic
EDAT- 2012/02/11 06:00
MHDA- 2013/04/20 06:00
CRDT- 2012/02/11 06:00
PHST- 2012/02/11 06:00 [entrez]
PHST- 2012/02/11 06:00 [pubmed]
PHST- 2013/04/20 06:00 [medline]
AID - 10.1111/j.1463-1326.2012.01582.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2012 Oct;14(10):869-81. doi: 
      10.1111/j.1463-1326.2012.01582.x. Epub 2012 Mar 8.