Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading
Abstract Prior work established that exercise alleviates muscle function loss in a clinically relevant rodent model mimicking the clinical sequelae of severely burned patients. On the basis of these data, we posit that pharmacologic treatment with insulin combined with exercise further mitigates los...
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| Format: | Article |
| Language: | English |
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Wiley
2019-07-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.14158 |
| _version_ | 1818283171280584704 |
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| author | Juquan Song Lisa A. Baer Melody R. S. Threlkeld Calvin Geng Charles E. Wade Steven E. Wolf |
| author_facet | Juquan Song Lisa A. Baer Melody R. S. Threlkeld Calvin Geng Charles E. Wade Steven E. Wolf |
| author_sort | Juquan Song |
| collection | DOAJ |
| description | Abstract Prior work established that exercise alleviates muscle function loss in a clinically relevant rodent model mimicking the clinical sequelae of severely burned patients. On the basis of these data, we posit that pharmacologic treatment with insulin combined with exercise further mitigates loss of muscle function following severe burn with immobilization. Twenty‐four Sprague–Dawley rats were assessed and trained to complete a climbing exercise. All rats followed a standardized protocol to mimic severe burn patients (40% total body surface area scald burn); all rats were immediately placed into a hindlimb unloading apparatus to simulate bedrest. The rats were then randomly assigned to four treatment groups: saline vehicle injection without exercise (VEH/NEX), insulin (5 U/kg) injection without exercise (INS/NEX), saline vehicle with daily exercise (VEH/EX), and insulin with daily exercise (INS/EX). The animals were assessed for 14 days following injury. The groups were compared for multiple variables. Isometric tetanic (Po) and twitch (Pt) forces were significantly elevated in the plantaris and soleus muscles of the INS/EX rats (P < 0.05). Genomic analysis revealed mechanistic causes with specific candidate changes. Molecular analysis of INS/EX rats revealed Akt phosphorylated by PDPK1 was increased with this treatment, and it further activated downstream signals mTOR, eEF2, and GSK3‐β (P < 0.05). Furthermore, muscle RING‐finger protein‐1 (MuRF‐1), an E3 ubiquitin ligase, was reduced in the INS/EX group (P < 0.05). Insulin and resistance exercise have a positive combined effect on the muscle function recovery in this clinically relevant rodent model of severe burn. Both treatments altered signaling pathways of increasing protein synthesis and decreasing protein degradation. |
| first_indexed | 2024-12-13T00:32:40Z |
| format | Article |
| id | doaj.art-ec2dcff54ccc49a188822bdf7719f398 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-13T00:32:40Z |
| publishDate | 2019-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-ec2dcff54ccc49a188822bdf7719f3982022-12-22T00:05:18ZengWileyPhysiological Reports2051-817X2019-07-01714n/an/a10.14814/phy2.14158Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloadingJuquan Song0Lisa A. Baer1Melody R. S. Threlkeld2Calvin Geng3Charles E. Wade4Steven E. Wolf5Department of Surgery University of Texas Medical Branch and Shriners Hospitals for Children Galveston TexasDepartment of Surgery University of Texas Health Science Center at Houston Houston TexasDepartment of Surgery University of Texas Southwestern Medical Center Dallas TexasDepartment of Surgery University of Texas Southwestern Medical Center Dallas TexasDepartment of Surgery University of Texas Health Science Center at Houston Houston TexasDepartment of Surgery University of Texas Medical Branch and Shriners Hospitals for Children Galveston TexasAbstract Prior work established that exercise alleviates muscle function loss in a clinically relevant rodent model mimicking the clinical sequelae of severely burned patients. On the basis of these data, we posit that pharmacologic treatment with insulin combined with exercise further mitigates loss of muscle function following severe burn with immobilization. Twenty‐four Sprague–Dawley rats were assessed and trained to complete a climbing exercise. All rats followed a standardized protocol to mimic severe burn patients (40% total body surface area scald burn); all rats were immediately placed into a hindlimb unloading apparatus to simulate bedrest. The rats were then randomly assigned to four treatment groups: saline vehicle injection without exercise (VEH/NEX), insulin (5 U/kg) injection without exercise (INS/NEX), saline vehicle with daily exercise (VEH/EX), and insulin with daily exercise (INS/EX). The animals were assessed for 14 days following injury. The groups were compared for multiple variables. Isometric tetanic (Po) and twitch (Pt) forces were significantly elevated in the plantaris and soleus muscles of the INS/EX rats (P < 0.05). Genomic analysis revealed mechanistic causes with specific candidate changes. Molecular analysis of INS/EX rats revealed Akt phosphorylated by PDPK1 was increased with this treatment, and it further activated downstream signals mTOR, eEF2, and GSK3‐β (P < 0.05). Furthermore, muscle RING‐finger protein‐1 (MuRF‐1), an E3 ubiquitin ligase, was reduced in the INS/EX group (P < 0.05). Insulin and resistance exercise have a positive combined effect on the muscle function recovery in this clinically relevant rodent model of severe burn. Both treatments altered signaling pathways of increasing protein synthesis and decreasing protein degradation.https://doi.org/10.14814/phy2.14158Genomic profileisometric forceprotein degradationprotein synthesissignal regulation |
| spellingShingle | Juquan Song Lisa A. Baer Melody R. S. Threlkeld Calvin Geng Charles E. Wade Steven E. Wolf Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading Physiological Reports Genomic profile isometric force protein degradation protein synthesis signal regulation |
| title | Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading |
| title_full | Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading |
| title_fullStr | Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading |
| title_full_unstemmed | Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading |
| title_short | Insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading |
| title_sort | insulin and exercise improved muscle function in rats with severe burns and hindlimb unloading |
| topic | Genomic profile isometric force protein degradation protein synthesis signal regulation |
| url | https://doi.org/10.14814/phy2.14158 |
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