{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:20:51Z","timestamp":1783549251848,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K10839"],"award-info":[{"award-number":["23K10839"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Diabetes Society Carrier Development Award"},{"DOI":"10.13039\/100016573","name":"Japan Association for Diabetes Education and Care","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016573","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008672","name":"Yamaguchi Endocrine research foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008672","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 1 diabetes mellitus is a major risk factor for both sarcopenia and osteoporosis, primarily due to the body\u2019s inability to utilize glucose as a result of insulin deficiency. Impairments in insulin and glucose signaling can accelerate the decline in muscle and bone health. To investigate this interaction, we examined whether insulin deficiency exacerbates muscle and bone deterioration in Chrebp knockout (KO) mice. Male wild-type (WT) and KO mice, aged 18 weeks, were intraperitoneally treated with 200 mg\/kg BW streptozotocin (STZ), which selectively destroys pancreatic beta cells, thereby inducing insulin deficiency. Two weeks after STZ administration, compared with STZ-treated WT mice, STZ-treated KO mice presented significantly greater reductions in body weight and gastrocnemius muscle weight (BW: WT-vehicle vs. WT-STZ; 2.58 [\u22121.23, 6.39] (p = 0.21); KO-vehicle vs. KO-STZ: 8.03 [5.23, 10.82]; GA muscle: WT vehicle vs. WT STZ: 0.084 [0.047, 0.12], p &lt; 0.0001; KO vehicle vs. KO STZ: 0.084, [0.047, 0.12], p &lt; 0.0001). The decrease in grip strength caused by STZ administration was greater in the KO mice than in the WT mice (mean differences [95% CIs]: WT vehicle\u2014WT STZ, 49.6. [0.9, 98.4], p = 0.046; WT STZ\u2014KO STZ: 71.40 [29.1, 113.7], p = 0.0059; KO vehicle\u2014KO STZ: 84.3 [51.9, 116.8], p = 0.0003). Consistent with these findings, STZ administration reduced IGF-1 expression and increased atrogin mRNA levels, with the highest levels in STZ-treated KO mice. In skeletal muscle, the changes in IGF-1 and Atrogen induced by STZ administration were significantly greater in the KO group than in the WT group (IGF-1: WT vehicle\u2014WT STZ: 0.19 [\u22120.072, 0.46], p = 0.17; KO vehicle\u2014KO STZ: 0.79 [0.53, 1.06], p &lt; 0.0001; Atrogen: WT vehicle\u2014WT STZ: \u22122.7 [\u22123.01, \u22122.29], p &lt; 0.0001; KO vehicle\u2014KO STZ: \u22123.35 [\u22123.71, \u22122.99], p &lt; 0.0001). The BMD in the Chrebp-deficient group was greater than that in the wild-type group (WT vehicle\u2014KO vehicle: \u22125.2 [\u22128.4, \u22121.9], p = 0.0014); however, the administration of STZ significantly decreased the BMD only in the KO group (WT vehicle\u2014WT STZ: p = 0.45, KO vehicle\u2014KO STZ: 7.2 [3.9, 10.4], p &lt; 0.0001). These results suggest that Chrebp deficiency combined with insulin deficiency aggravates sarcopenia and osteoporosis risk. Therefore, insulin and glucose signals are important for maintaining muscle and bone mass and function. However, further studies are needed to elucidate the mechanisms by which ChREBP deletion and insulin deficiency cause osteosarcopenia.<\/jats:p>","DOI":"10.3390\/ijms262311672","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:39:43Z","timestamp":1764679183000},"page":"11672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Insulin Deficiency Exacerbates Muscle Atrophy and Osteopenia in Chrebp Knockout Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6547-9732","authenticated-orcid":false,"given":"Chihiro","family":"Ushiroda","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mioko","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risako","family":"Yamamoto-Wada","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Deguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihomi","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-1893","authenticated-orcid":false,"given":"Toshinori","family":"Imaizumi","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9099-3493","authenticated-orcid":false,"given":"Yusuke","family":"Seino","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0807-199X","authenticated-orcid":false,"given":"Atsushi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Yabe","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9837-6238","authenticated-orcid":false,"given":"Katsumi","family":"Iizuka","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Fujita Health University, Toyoake 470-1192, Japan"},{"name":"Food and Nutrition Service Department, Fujita Health University Hospital, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Buschard, K. 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