Abstract | BACKGROUND: METHODS: RESULTS: After 12-month treatment, there were no significant differences in systolic and diastolic blood pressures decreases, plasma fasting blood glucose and HbA1c between the 2 groups. Compared with amlodipine group, fasting blood insulin levels and insulin resistance index (HOMA-IR) were significantly decreased in losartan group, and in addition, the circulating levels of 8-OHdG and NT were significantly decreased in losartan group, while the serum SOD activity was enhanced. There were significant positively correlations of HOMA-IR with inflammatory oxidative stress markers. In vitro study showed that losartan could increase glucose uptake in 3T3-L1 adipocytes (P<0.01) and decrease adipocyte size (P<0.01), while amlodipine can't. Losartan can also enhance adiponectin (P<0.05) and decrease TNF-α (P<0.05) and IL-6 (P<0.01) secretion, while amlodipine can't. The protein expressions of pIR, IRS-1 and PI3K were significantly increased after treatment with losartan (P<0.01), while the level of IRS-1 serine phosphorylation was decreased (P<0.01), which could be blocked by specific PI3K inhibitor wortmannin. CONCLUSIONS: These results suggest that the effect of losartan on insulin resistance is associated with the reduction of oxidative stress and inflammation in patients with type 2 DKD as well as the activation of insulin signal pathway in insulin-resistance 3T3-L1 adipocytes through modulation of PI3K pathway. (Clinical Trials. gov number, NCT 00774904).
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Authors | Y Pan, Q Y Qiao, L H Pan, D C Zhou, C Hu, H F Gu, S K Fu, X L Liu, H M Jin |
Journal | Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
(Exp Clin Endocrinol Diabetes)
Vol. 123
Issue 3
Pg. 170-7
(Mar 2015)
ISSN: 1439-3646 [Electronic] Germany |
PMID | 25502581
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © Georg Thieme Verlag KG Stuttgart · New York. |
Chemical References |
- Antihypertensive Agents
- Amlodipine
- Receptor, Insulin
- Losartan
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Topics |
- 3T3-L1 Cells
- Adipocytes
(drug effects)
- Aged
- Amlodipine
(administration & dosage, pharmacology)
- Animals
- Antihypertensive Agents
(administration & dosage, pharmacology)
- Diabetic Nephropathies
(drug therapy)
- Humans
- Insulin Resistance
(physiology)
- Losartan
(administration & dosage, pharmacology)
- Male
- Mice
- Middle Aged
- Oxidative Stress
(drug effects)
- Receptor, Insulin
(metabolism)
- Signal Transduction
(drug effects)
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