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- Title
Telmisartan Improves Insulin Resistance by Increasing Apoptosis of Fat Cells and Decreasing Macrophage Infiltration in High Fat-fed Mice.
- Authors
Fujisaka, Shiho; Usui, Isao; Yamazaki, Yu; Bukhari, Agussalim; Kanatani, Yukiko; Suzuki, Hikari; He, Jianying; Ishiki, Manabu; Iwata, Minoru; Hiratani, Kazuyuki; Urakaze, Masaharu; Kobayashi, Masashi
- Abstract
AngiotensinII receptor blocker (ARB), a class of anti-hypertensive drug, is known to have beneficial effects on insulin resistance. Telmisartan, a new ARB, has another function as a partial agonist of PPARγ, which may be associated to its stronger effect to improve insulin sensitivity than the other ARBs. We have also reported that Telmisartsn improves insulin sensitivity with reduced body weight and adipoeyte size in high fat-fed mice. To further clarify the underlying mechanisms, we investigated the effects of Telmisartan on apoptosis, macrophage infiltration and cytokine production in adipose tissues of obese insulin resistant mice. C57BL mice were fed normal diet (ND) or high fat diet (HFD) for 24 weeks and then Telmisartan was orally administered for 5 weeks. Pioglitazone Or Candesartan were also administered as controls. Intraperitoneal insulin tolerance test (ITT), glucose tolerance test (GTT), HOMA-IR, weight of adipose tissue, adipocyte size, macrophage infiltration and apoptosis in adipose tissue were measured by standard technique. In HFD mice, glucose profiles were improved by either Telmisartan or Pioglitazone. HOMA-IR was reduced by Telmisartan by 19%. The average of adipocyte size in HFD mice was decreased by Telmisartan and Candesartan by 36% and 7%, respectively. The number of macrophages in adipose tissue was 5 times more in HFD mice, which was decreased by 65% and 20% by Telmisartan and Candesartan, respectively. TNFα mRNA in adipose tissue was reduced by 70% by Telmisartan in HFD mice. The number of apoptotic cells was less in HFD mice, and Telmisartan increased it. Telmisartan improved insulin resistance of HFD mice with reduced adipocyte size, infiltration of macrophages and TNFα level in adipose tissue. Enhancement of apoptosis in adipose tissue may be a part of the mechanisms for decreased adipocyte size and improvement of insulin resistance by Telmisartan.
- Subjects
ANGIOTENSIN II; INSULIN resistance; FAT cells; MACROPHAGES; APOPTOSIS; ADIPOSE tissues; LABORATORY mice
- Publication
Diabetes, 2007, Vol 56, pA453
- ISSN
0012-1797
- Publication type
Article