Angiotensin II Enhances Insulin Sensitivity in Vitro and in Vivo

• Published in: Endocrinology (Philadelphia) 2005-05, Vol.146 (5), p.2246-2254
• Main Authors: Juan, Chi-Chang, Chien, Yueh, Wu, Liang-Yi, Yang, Wei-Ming, Chang, Chih-Ling, Lai, Ying-Hsiu, Ho, Pei-Hsuan, Kwok, Ching Fai, Ho, Low-Tone
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - chemistry; Adipocytes - drug effects; Adipocytes - metabolism; Adipose tissue; AKT protein; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensinogen; Animals; Binding; Biological and medical sciences; Blood Glucose - analysis; Drug Synergism; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Gene Expression; Glucose; Glucose - metabolism; Glucose Tolerance Test; Glucose transporter; Glucose Transporter Type 4; Hormones. Régulation; Hypertension; In vivo methods and tests; Insulin; Insulin - blood; Insulin - metabolism; Insulin - pharmacology; Insulin Resistance; Intracellular signalling; Losartan - pharmacology; Male; Monosaccharide Transport Proteins - metabolism; Muscle Proteins - metabolism; Obesity; Pathogenesis; Phosphorylation; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - physiology; Receptor, Angiotensin, Type 2 - genetics; Receptor, Angiotensin, Type 2 - physiology; Receptor, Insulin - drug effects; Receptor, Insulin - metabolism; Receptors; Renin; Reverse Transcriptase Polymerase Chain Reaction; Sensitizing; Signal Transduction - drug effects; Translocation; Tyrosine; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2004-1136

The renin-angiotensin system plays a critical role in the pathogenesis of obesity, obesity-associated hypertension, and insulin resistance. However, the biological actions of angiotensin II (AII) on insulin sensitivity remain controversial. Because angiotensinogen and AII receptors are expressed on adipose tissue, we investigated the effect of AII on the insulin sensitivity of isolated rat adipocytes. The results of a receptor binding assay showed the maximal AII binding capacity of adipocytes to be 8.3 ± 0.9 fmol/7 × 106 cells and the dissociation constant to be 2.72 ± 0.11 nm. Substantial expression of both type 1 and 2 AII (AT1 and AT2) receptors was detected by RT-PCR. AII had no effect on basal glucose uptake, but significantly potentiated insulin-stimulated glucose uptake; this effect was abolished by the AT1 antagonist, losartan. In addition, AII did not alter the insulin binding capacity of adipocytes, but increased insulin-stimulated tyrosine phosphorylation of the insulin receptor β-subunit, Akt phosphorylation, and translocation of glucose transporter 4 to the plasma membrane. AII potentiated insulin-stimulated glucose uptake through the AT1 receptor and by alteration of the intracellular signaling of insulin. Intraperitoneal injection of Sprague Dawley rats with AII increased insulin sensitivity in vivo. In conclusion, we have shown that AII enhances insulin sensitivity both in vitro and in vivo, suggesting that dysregula-tion of the insulin-sensitizing effect of AII may be involved in the development of insulin resistance.