Blockade of glucagon increases muscle mass and alters fiber type composition in mice deficient in proglucagon‐derived peptides
| Title: | Blockade of glucagon increases muscle mass and alters fiber type composition in mice deficient in proglucagon‐derived peptides |
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| Authors: | Shinji Ueno, Yusuke Seino, Shihomi Hidaka, Masashi Nakatani, Keisuke Hitachi, Naoya Murao, Yasuhiro Maeda, Haruki Fujisawa, Megumi Shibata, Takeshi Takayanagi, Katsumi Iizuka, Daisuke Yabe, Yoshihisa Sugimura, Kunihiro Tsuchida, Yoshitaka Hayashi, Atsushi Suzuki |
| Source: | Journal of Diabetes Investigation, Vol 14, Iss 9, Pp 1045-1055 (2023) |
| Publisher Information: | Wiley, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Diseases of the endocrine glands. Clinical endocrinology |
| Subject Terms: | Amino acid, Glucagon, Skeletal muscle, Diseases of the endocrine glands. Clinical endocrinology, RC648-665 |
| More Details: | ABSTRACT Aims/Introduction Glucagon is secreted from pancreatic α‐cells and plays an important role in amino acid metabolism in liver. Various animal models deficient in glucagon action show hyper‐amino acidemia and α‐cell hyperplasia, indicating that glucagon contributes to feedback regulation between the liver and the α‐cells. In addition, both insulin and various amino acids, including branched‐chain amino acids and alanine, participate in protein synthesis in skeletal muscle. However, the effect of hyperaminoacidemia on skeletal muscle has not been investigated. In the present study, we examined the effect of blockade of glucagon action on skeletal muscle using mice deficient in proglucagon‐derived peptides (GCGKO mice). Materials and Methods Muscles isolated from GCGKO and control mice were analyzed for their morphology, gene expression and metabolites. Results GCGKO mice showed muscle fiber hypertrophy, and a decreased ratio of type IIA and an increased ratio of type IIB fibers in the tibialis anterior. The expression levels of myosin heavy chain (Myh) 7, 2, 1 and myoglobin messenger ribonucleic acid were significantly lower in GCGKO mice than those in control mice in the tibialis anterior. GCGKO mice showed a significantly higher concentration of arginine, asparagine, serine and threonine in the quadriceps femoris muscles, and also alanine, aspartic acid, cysteine, glutamine, glycine and lysine, as well as four amino acids in gastrocnemius muscles. Conclusions These results show that hyperaminoacidemia induced by blockade of glucagon action in mice increases skeletal muscle weight and stimulates slow‐to‐fast transition in type II fibers of skeletal muscle, mimicking the phenotype of a high‐protein diet. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2040-1124 2040-1116 |
| Relation: | https://doaj.org/toc/2040-1116; https://doaj.org/toc/2040-1124 |
| DOI: | 10.1111/jdi.14032 |
| Access URL: | https://doaj.org/article/f41781e00b1a43f5ac0ed9f6d6341b45 |
| Accession Number: | edsdoj.f41781e00b1a43f5ac0ed9f6d6341b45 |
| Database: | Directory of Open Access Journals |
| ISSN: | 20401124 20401116 |
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| DOI: | 10.1111/jdi.14032 |
| Published in: | Journal of Diabetes Investigation |
| Language: | English |