Abstract | AIM: METHODS: RESULTS: 2922 was effective in reducing 11beta-HSD1 activity in inguinal adipose tissue (>90% for 100 mg/kg) and was efficacious in improving glucose homeostasis at doses > or =10 mg/kg. Plasma insulin, blood glucose, glucose tolerance and homeostatic model assessment indices were all improved in mice treated with 2922 (100 mg/kg) compared with control animals. Despite an improvement in these parameters, no differences were observed in body weight, adipose or lean tissue masses in the 2922-treated mice. Interestingly, circulating lipids, proinflammatory cytokines and atherosclerosis were unaltered in response to 2922, although a small reduction in LDL cholesterol was detected. CONCLUSIONS: Importantly, 11beta-HSD1 inhibition leads to improved glucose metabolism and does not result in a worsening of atherosclerotic lesion area, yet retained antidiabetic potential in the face of multiple severe metabolic aberrations. This study reinforces the potential use of 11beta-HSD1 inhibitors in patients with the metabolic syndrome without negatively impacting atherosclerosis.
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Authors | D J Lloyd, J Helmering, D Cordover, M Bowsman, M Chen, C Hale, P Fordstrom, M Zhou, M Wang, S A Kaufman, M M Véniant |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 11
Issue 7
Pg. 688-99
(Jul 2009)
ISSN: 1463-1326 [Electronic] England |
PMID | 19527482
(Publication Type: Journal Article)
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Chemical References |
- Blood Glucose
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Hypoglycemic Agents
- Insulin
- Thiazolidinediones
- Triglycerides
- Rosiglitazone
- Cholesterol
- Simvastatin
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
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Topics |
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
(antagonists & inhibitors)
- Adipose Tissue
(drug effects)
- Animals
- Atherosclerosis
(complications, drug therapy)
- Blood Glucose
(analysis)
- Body Composition
(drug effects)
- Body Weight
(drug effects)
- Cholesterol
(blood)
- Diabetes Mellitus, Type 2
(complications, drug therapy)
- Disease Models, Animal
- Dyslipidemias
(complications, drug therapy)
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(therapeutic use)
- Hypoglycemic Agents
(therapeutic use)
- Insulin
(blood)
- Male
- Metabolic Syndrome
(complications, drug therapy)
- Mice
- Mice, Knockout
- Rosiglitazone
- Simvastatin
(pharmacology)
- Thiazolidinediones
(therapeutic use)
- Triglycerides
(blood)
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