| Blockade of Cannabinoid Receptor 1 Improves Insulin Resistance, Lipid Metabolism, and Diabetic Nephropathy in db/db Mice. | |
| | |
MedLine Citation:
|
PMID: 22234468 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The endocannabinoid system is important in the pathogenesis of obesity-related metabolic disorders. However, the effect of inhibiting the endocannabinoid system in type 2 diabetic nephropathy is unclear. Therefore, we examined the effect of the cannabinoid (CB)1 receptor antagonist, SR141716, on insulin resistance and diabetic nephropathy in db/db mice. Six-week-old db/db mice were treated with the CB1-specific antagonist SR141716 (10 mg/kg·d) for 3 months. Treatment with SR141716 significantly improved insulin resistance and lipid abnormalities. Concomitantly, CB1 antagonism improved cardiac functional and morphological abnormality, hepatic steatosis, and phenotypic changes of adipocytes into small differentiated forms, associated with increased adiponectin expression and decreased lipid hydroperoxide levels. CB1 receptor was overexpressed in diabetic kidneys, especially in podocytes. Treatment with the SR141716 markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic and proinflammatory cytokine synthesis. Furthermore, SR141716 improved renal lipid metabolism and decreased urinary 8-isoprostane levels, renal lipid hydroperoxide content, and renal lipid content. In cultured podocytes, high-glucose stimulation increased CB1 receptor expression, and SR141716 treatment abolished high-glucose-induced up-regulation of collagen and plasminogen activator inhibitor-1 synthesis. Additionally, knockdown of CB1 receptor expression by stealth small interfering RNA abolished high-glucose-induced sterol-regulatory element-binding protein-1 expression in podocytes. These findings suggest that CB1 blockade improves insulin resistance and protect against renal injury through both metabolic and antifibrotic effects in type 2 diabetic nephropathy. Targeting CB1 blockade could therefore provide a new therapeutic target to prevent type 2 diabetic nephropathy. |
| | |
Authors:
|
D H Nam; M H Lee; J E Kim; H K Song; Y S Kang; J E Lee; H W Kim; J J Cha; Y Y Hyun; S H Kim; S Y Han; K H Han; J Y Han; Dae Ryong Cha |
Related Documents
:
|
17065678 - Design and validation of a population-based definition of the metabolic syndrome. 8383698 - Deletion of mitochondrial dna in a case of early-onset diabetes mellitus, optic atrophy... 21249428 - Impaired mir-146a expression links subclinical inflammation and insulin resistance in t... 16856438 - Clinical pictures of type 2 diabetes in thai children and adolescents is highly related... 8502658 - Nutritional regulation of insulin-sensitive glucose transporter gene expression in rat ... 6290138 - Hormonal effects on the liver glucose metabolism in rainbow trout (salmo gairdneri). |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-10 |
Journal Detail:
|
Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-11 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Internal Medicine (D.H.N., M.H.L., J.E.K., H.K.S., Y.S.K., J.J.C., Y.Y.H., D.R.C.), Division of Nephrology, Korea University, Ansan City 425-020, Korea; Department of Internal Medicine (J.E.L., H.W.K.), Division of Nephrology, Wonkwang University, Gunpo City 435-040, Korea; Department of Internal Medicine (S.H.K.), Division of Cardiology, Korea University, Ansan City 425-020, Korea; Department of Internal Medicine (S.Y.H., K.H.H.), Division of Nephrology, Inje University, Goyang City 411-706, Korea; and Department of Pathology (J.Y.H.), Inha University, Incheon, Incheon City 400-711, Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Differential regulation of glucose transporters mediated by CRH receptor type 1 and type 2 in human ...
Next Document: Activation of Latent Human GDF9 by a Single Residue Change (Gly391Arg) in the Mature Domain.