title: Angiotensin II enhances insulin sensitivity in vitro and in vivo.
abstract: 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 x 10(6) 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 beta-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 dysregulation of the insulin-sensitizing effect of AII may be involved in the development of insulin resistance.
authors.affiliation: Institute of Physiology, National Yang-Ming University, and Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Juan
authors.forename: Yueh
authors.initials: Y
authors.lastname: Chien
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Wu
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Yang
authors.forename: Chih-Ling
authors.initials: CL
authors.lastname: Chang
authors.forename: Ying-Hsiu
authors.initials: YH
authors.lastname: Lai
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Ho
authors.forename: Ching Fai
authors.initials: CF
authors.lastname: Kwok
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
mesh_terms: D017667:Adipocytes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004357:Drug Synergism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000502:physiology; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C495694:Slc2a4 protein, rat; D000804:Angiotensin II; D011972:Receptor, Insulin; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D019808:Losartan