An angiotensin II AT₁ receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3‐L1 adipocytes

Abstract

Evidence has accumulated that some of the angiotensin II AT1 receptor antagonists have insulin-sensitizing property. We thus examined the effect of telmisartan on insulin action using 3T3-L1 adipocytes. With standard differentiation inducers, a higher dose of telmisartan effectively facilitated differentiation of 3T3-L1 preadipocytes. Treatment of both differentiating adipocytes and fully differentiated adipocytes with telmisartan caused a dose-dependent increase in mRNA levels for PPARgamma target genes such as aP2 and adiponectin. By contrast, telmisartan attenuated 11beta-hydroxysteroid dehydrogenase type 1 mRNA level in differentiated adipocytes. Of note, we demonstrated for the first time that telmisartan augmented GLUT4 protein expression and 2-deoxy glucose uptake both in basal and insulin-stimulated state of adipocytes, which may contribute, at least partly, to its insulin-sensitizing ability.

Angiotensin II type 1 receptor-independent beneficial effects of telmisartan on dietary-induced obesity, insulin resistance and fatty liver in mice

“…Recently, it was shown to be a partial agonist of the peroxisome proliferatoractivated receptor (PPAR)γ in cultured cells [3,4] and to activate PPARα in cultured hepatic cells and in liver of wild-type mice fed a high-fat diet (HFD) [5]. Telmisartan has also been reported to improve HFD-induced obesity, insulin resistance and fatty liver in wild-type animals [4,5].…”

Comparative Effects of Telmisartan and Valsartan on Insulin Resistance in Hypertensive Patients with Metabolic Syndrome

“…This effect may be related to the insulin-sensitizing effect of telmisartan in our study. On the other hand, recent studies have shown that telmisartan ameliorated mitochondrial energy metabolism in skeletal muscle and enhanced glucose uptake in adipocytes accompanied by an increase in GLUT4 expression (12,13) F i g u r e 1 . Ch a n g e s i n h o me o s t a s i s mo d e l a s s e s s me n t o f i n s u l i n r e s i s t a n c e ( HOMA-R) a f t e r 4 we e k s o f t e l mi s a r t a n a n d v a l s a r t a n a d mi n i s t r a t i o n . …”

Structural basis for telmisartan-mediated partial activation of PPAR gamma

“…Indeed, a number of clinical and experimental studies have already been conducted, which provide evidence for the beneficial effects of telmisartan in cases of type 2 diabetes, as well as metabolic syndrome and obesity. [14][15][16][17][18][19][20] Although the molecular mechanism required for the selective PPARg modulator phenotype is still unknown, partial agonism is assumed to be a typical and essential characteristic of selective PPARg modulator. 9,13 Telmisartan exhibits this critical feature, 9 and here we describe a crystal structure of human PPARg in complex with telmisartan that clarifies the mechanism of partial agonism.…”