Abstract | OBJECTIVES: The role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 ( C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue. METHODS: RESULTS: Treatment with C21 ameliorated insulin resistance in KK-Ay mice without influencing blood pressure, at least partially through effects on the PPARγ pathway. C21 treatment increased serum adiponectin concentration and decreased TNF-α concentration; however, these effects were attenuated by PPARγ blockade by co-treatment with GW9662. Moreover, we observed that administration of C21 enhanced adipocyte differentiation and PPARγ DNA-binding activity, with a decrease in inflammation in white adipose tissue, whereas these effects of C21 were attenuated by co-treatment with GW9662. We also observed that administration of C21 restored β cell damage in diabetic pancreatic tissue. CONCLUSION: The present study demonstrated that direct AT(2) receptor stimulation by C21 accompanied with PPARγ activation ameliorated insulin resistance in T2DM mice, at least partially due to improvement of adipocyte dysfunction and protection of pancreatic β cells.
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Authors | Kousei Ohshima, Masaki Mogi, Fei Jing, Jun Iwanami, Kana Tsukuda, Li-Juan Min, Akiyoshi Ogimoto, Björn Dahlöf, Ulrike M Steckelings, Tomas Unger, Jitsuo Higaki, Masatsugu Horiuchi |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 11
Pg. e48387
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23155382
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2-chloro-5-nitrobenzanilide
- Adiponectin
- Anilides
- Blood Glucose
- Insulin
- N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide
- PPAR gamma
- Receptor, Angiotensin, Type 2
- Sulfonamides
- Thiophenes
- Tumor Necrosis Factor-alpha
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Topics |
- Adiponectin
(blood)
- Adipose Tissue
(drug effects, metabolism)
- Anilides
(pharmacology)
- Animals
- Blood Glucose
(drug effects, metabolism)
- Diabetes Mellitus, Experimental
(metabolism)
- Diabetes Mellitus, Type 2
(metabolism)
- Inflammation
(metabolism)
- Insulin
(blood)
- Insulin Resistance
(physiology)
- Male
- Mice
- PPAR gamma
(antagonists & inhibitors, metabolism)
- Pancreas
(drug effects, metabolism)
- Receptor, Angiotensin, Type 2
(agonists)
- Sulfonamides
(pharmacology)
- Thiophenes
(pharmacology)
- Tumor Necrosis Factor-alpha
(blood)
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