Effects of telmisartan and valsartan on insulin sensitivity in obese diabetic mice

Ushijima, Kazuo; Takuma, Masashi; Ando, Hitoshi; Ishikawa-Kobayashi, Eiko; Nozawa, Masahiko; Maekawa, Toshiro; Shiga, Tsuyoshi; Fujimura, Akio

doi:10.1016/j.ejphar.2012.11.022

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…A recent meta-analysis data revealed that telmisartan improves insulin resistance in patients with hypertension [10]. It was also reported that telmisartan has beneficial effects on insulin resistance in skeletal muscles and adipose tissues [12,13]. Based on the previous reports, therefore, our results suggest that the beneficial effects of telmisartan on glycemic control may be mediated by its actions on other insulin target organs such as the skeletal muscles and adipose tissues rather than the liver.…”

Section: Discussionsupporting

confidence: 68%

“…Unlike other ARBs, telmisartan exhibits various ancillary effects including improvement of insulin resistance and cardiometabolic profile [9-11]. Telmisartan is reported to improve insulin resistance in skeletal muscles via peroxisome proliferated-activated receptor δ (PPARδ) [12], and adipose tissues by elevating adiponectin and reducing pro-inflammatory cytokines [13]. However, the effects of telmisartan on hepatic glucose production (HGP) and its underlying mechanism have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Telmisartan increases hepatic glucose production via protein kinase C ζ-dependent insulin receptor substrate-1 phosphorylation in HepG2 cells and mouse liver

Cho

2019

Yeungnam Univ J Med

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BackgroundDysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice.MethodsGlucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase α (G6Pase-α), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ζ (PKCζ) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice.ResultsTelmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a 40 μM concentration without a change in G6Pase-α expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 (p-IRS-1-Ser302) and decreased p-IRS-1-Tyr632 dose-dependently. Telmisartan dose-dependently increased p-PKCζ-Thr410 which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative PKCζ significantly attenuated telmisartan-induced HGP and p-IRS-1-Ser302 and -inhibited p-IRS-1-Tyr632. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased p-IRS-1-Ser302 and decreased p-IRS-1-Tyr632, which was accompanied by an increase in p-PKCζ-Thr410. ConclusionThese results suggest that telmisartan increases HGP by inducing p-PKCζ-Thr410 that increases p-IRS-1-Ser302 and decreases p-IRS-1-Tyr632 in a PPARγ-independent manner.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Telmisartan increases hepatic glucose production via protein kinase C ζ-dependent insulin receptor substrate-1 phosphorylation in HepG2 cells and mouse liver

Cho

2019

Yeungnam Univ J Med

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“…These results have suggested that blockade of Ang II receptors may be animportant treatment option in the management of chronicasthma. Moreover, the predominant effect of telmisartan reported in the present study may be attributed to other mechanisms specifically utilized by telmisartan, including effective PPAR-γ activation [28], while valsartan lacks such activity [29]. According to the outcome of the present study, the antiinflammatory activity of telmisartan may not be attributed to the Ag II receptor blockade only, and other mechanisms might be involved including PPAR-γ agonist activity.…”

Section: Discussionsupporting

confidence: 46%

Effects of Valsartan and Telmisartan on the LungTissue Histology in Sensitized Rats

Algaem¹,

Numan²,

Hussain³

2013

AJPS

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The renin-angiotensin system (RAS)was potentially implicated in the pathogenesis of pulmonary disorders through its involvement in inducing pro-inflammatory mediators in the lung tissues. The present study evaluates the effects of the angiotensin receptor blockers (ARBs), telmisartan and valsartan, on the histological changes of lung tissues in sensitized rats. Twenty-fourWister female rats were randomly divided into four groups: A, negative control; B, valsartan-treated group; C, telmisartan-treated group and D, positive control. The rats in the groups B-D were sensitized and challenged with ovalbumin (OVA). Group A rats were sensitized and challenged with normal saline. Rats from groups B and C were treated with either valsartan or telmisartan (5mg/kg/day), respectively. The effects of administered ARBs on lung tissue structures were histologically evaluated. Treatment with telmisartan significantly attenuates the inflammatory and the hyper-proliferative changes in lung tissue after OVA-challenge, while valsartan did not show such effect. In conclusion, telmisartan demonstrates anti-inflammatory and anti-proliferative activities in sensitized rats, while valsartan lacks these effects.

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“…Moreover, partial activation of PPARγ in WAT causes apoptosis of mature and large adipocytes and increases the number of small adipocytes (Ushijima et al . ), thereby explaining the reduction of subcutaneous and intra‐abdominal fat pad masses and the decreased adiposity index in obese mice treated with TEL (Renne et al . ).…”

Section: Discussionmentioning

confidence: 99%

Enhanced pan‐peroxisome proliferator‐activated receptor gene and protein expression in adipose tissue of diet‐induced obese mice treated with telmisartan

Penna-de-Carvalho

Graus-Nunes

Rabelo-Andrade

et al. 2014

Experimental Physiology

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New Findings r What is the central question of this study?Telmisartan, an antihypertensive, has beneficial side-effects through its peroxisome proliferator-activated receptor (PPAR) β/δ agonism in white adipose tissue, besides its well-known property of partial PPARγ agonism. Here, we investigated a potential pan-PPAR role of this drug in the white and brown adipose tissues. r What is the main finding and its importance? A. Penna-de-Carvalho and others telmisartan ameliorates inflammation and insulin resistance, as well as inducing non-shivering thermogenesis. Our results point to new therapeutic targets for the control of obesity and comorbidities through pan-PPAR-related effects.

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Effects of telmisartan and valsartan on insulin sensitivity in obese diabetic mice

Cited by 14 publications

References 34 publications

Telmisartan increases hepatic glucose production via protein kinase C ζ-dependent insulin receptor substrate-1 phosphorylation in HepG2 cells and mouse liver

Telmisartan increases hepatic glucose production via protein kinase C ζ-dependent insulin receptor substrate-1 phosphorylation in HepG2 cells and mouse liver

Effects of Valsartan and Telmisartan on the LungTissue Histology in Sensitized Rats

Enhanced pan‐peroxisome proliferator‐activated receptor gene and protein expression in adipose tissue of diet‐induced obese mice treated with telmisartan

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