IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle
IRW (Isoleucine–Arginine–Tryptophan), has antihypertensive and anti-inflammatory properties in cells and animal models and prevents angiotensin-II- and tumor necrosis factor (TNF)-α-induced insulin resistance (IR) in vitro. We investigated the effects of IRW on body composition, glucose homeostasis...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/6/1235 |
| _version_ | 1827662201981239296 |
|---|---|
| author | Stepheny C. de Campos Zani Myoungjin Son Khushwant S. Bhullar Catherine B. Chan Jianping Wu |
| author_facet | Stepheny C. de Campos Zani Myoungjin Son Khushwant S. Bhullar Catherine B. Chan Jianping Wu |
| author_sort | Stepheny C. de Campos Zani |
| collection | DOAJ |
| description | IRW (Isoleucine–Arginine–Tryptophan), has antihypertensive and anti-inflammatory properties in cells and animal models and prevents angiotensin-II- and tumor necrosis factor (TNF)-α-induced insulin resistance (IR) in vitro. We investigated the effects of IRW on body composition, glucose homeostasis and insulin sensitivity in a high-fat diet (HFD) induced insulin resistant (IR) model. C57BL/6 mice were fed HFD for 6 weeks, after which IRW was incorporated into the diet (45 or 15 mg/kg body weight (BW)) until week 14. IRW45 (at a dose of 45 mg/kg BW) reduced BW (<i>p</i> = 0.0327), fat mass gain (<i>p</i> = 0.0085), and preserved lean mass of HFD mice (<i>p</i> = 0.0065), concomitant with enhanced glucose tolerance and reduced fasting glucose (<i>p</i> < 0.001). In skeletal muscle, IRW45 increased insulin-stimulated protein kinase B (AKT) phosphorylation (<i>p</i> = 0.0132) and glucose transporter 4 (GLUT4) translocation (<i>p</i> < 0.001). Angiotensin 2 receptor (AT2R) (<i>p</i> = 0.0024), phosphorylated 5′-AMP-activated protein kinase (AMPKα) (<i>p</i> < 0.0124) and peroxisome proliferator-activated receptor gamma (PPARγ) (<i>p</i> < 0.001) were enhanced in skeletal muscle of IRW45-treated mice, as was the expression of genes involved in myogenesis. Plasma angiotensin converting enzyme-2 (ACE2) activity was increased (<i>p</i> = 0.0016). Uncoupling protein-1 in white adipose tissue (WAT) was partially restored after IRW supplementation. IRW improves glucose tolerance and body composition in HFD-fed mice and promotes glucose uptake in skeletal muscle via multiple signaling pathways, independent of angiotensin converting enzyme (ACE) inhibition. |
| first_indexed | 2024-03-10T00:21:49Z |
| format | Article |
| id | doaj.art-6b2f18e7116448a6b9871d61deb0def1 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:21:49Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6b2f18e7116448a6b9871d61deb0def12023-11-23T15:41:16ZengMDPI AGBiomedicines2227-90592022-05-01106123510.3390/biomedicines10061235IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal MuscleStepheny C. de Campos Zani0Myoungjin Son1Khushwant S. Bhullar2Catherine B. Chan3Jianping Wu4Department of Physiology, University of Alberta, Edmonton, AB T6G 2H7, CanadaDepartment of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, CanadaDepartment of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB T6G 2H7, CanadaDepartment of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, CanadaIRW (Isoleucine–Arginine–Tryptophan), has antihypertensive and anti-inflammatory properties in cells and animal models and prevents angiotensin-II- and tumor necrosis factor (TNF)-α-induced insulin resistance (IR) in vitro. We investigated the effects of IRW on body composition, glucose homeostasis and insulin sensitivity in a high-fat diet (HFD) induced insulin resistant (IR) model. C57BL/6 mice were fed HFD for 6 weeks, after which IRW was incorporated into the diet (45 or 15 mg/kg body weight (BW)) until week 14. IRW45 (at a dose of 45 mg/kg BW) reduced BW (<i>p</i> = 0.0327), fat mass gain (<i>p</i> = 0.0085), and preserved lean mass of HFD mice (<i>p</i> = 0.0065), concomitant with enhanced glucose tolerance and reduced fasting glucose (<i>p</i> < 0.001). In skeletal muscle, IRW45 increased insulin-stimulated protein kinase B (AKT) phosphorylation (<i>p</i> = 0.0132) and glucose transporter 4 (GLUT4) translocation (<i>p</i> < 0.001). Angiotensin 2 receptor (AT2R) (<i>p</i> = 0.0024), phosphorylated 5′-AMP-activated protein kinase (AMPKα) (<i>p</i> < 0.0124) and peroxisome proliferator-activated receptor gamma (PPARγ) (<i>p</i> < 0.001) were enhanced in skeletal muscle of IRW45-treated mice, as was the expression of genes involved in myogenesis. Plasma angiotensin converting enzyme-2 (ACE2) activity was increased (<i>p</i> = 0.0016). Uncoupling protein-1 in white adipose tissue (WAT) was partially restored after IRW supplementation. IRW improves glucose tolerance and body composition in HFD-fed mice and promotes glucose uptake in skeletal muscle via multiple signaling pathways, independent of angiotensin converting enzyme (ACE) inhibition.https://www.mdpi.com/2227-9059/10/6/1235ACEbioactive peptidesIRWinsulin resistanceobesity |
| spellingShingle | Stepheny C. de Campos Zani Myoungjin Son Khushwant S. Bhullar Catherine B. Chan Jianping Wu IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle Biomedicines ACE bioactive peptides IRW insulin resistance obesity |
| title | IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle |
| title_full | IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle |
| title_fullStr | IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle |
| title_full_unstemmed | IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle |
| title_short | IRW (Isoleucine–Arginine–Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle |
| title_sort | irw isoleucine arginine tryptophan improves glucose tolerance in high fat diet fed c57bl 6 mice via activation of insulin signaling and ampk pathways in skeletal muscle |
| topic | ACE bioactive peptides IRW insulin resistance obesity |
| url | https://www.mdpi.com/2227-9059/10/6/1235 |
| work_keys_str_mv | AT stephenycdecamposzani irwisoleucineargininetryptophanimprovesglucosetoleranceinhighfatdietfedc57bl6miceviaactivationofinsulinsignalingandampkpathwaysinskeletalmuscle AT myoungjinson irwisoleucineargininetryptophanimprovesglucosetoleranceinhighfatdietfedc57bl6miceviaactivationofinsulinsignalingandampkpathwaysinskeletalmuscle AT khushwantsbhullar irwisoleucineargininetryptophanimprovesglucosetoleranceinhighfatdietfedc57bl6miceviaactivationofinsulinsignalingandampkpathwaysinskeletalmuscle AT catherinebchan irwisoleucineargininetryptophanimprovesglucosetoleranceinhighfatdietfedc57bl6miceviaactivationofinsulinsignalingandampkpathwaysinskeletalmuscle AT jianpingwu irwisoleucineargininetryptophanimprovesglucosetoleranceinhighfatdietfedc57bl6miceviaactivationofinsulinsignalingandampkpathwaysinskeletalmuscle |