{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:34:07Z","timestamp":1789439647458,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["FRGS\/1\/2015\/SKK10\/IMU\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2015\/SKK10\/IMU\/02\/1"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL\/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg\/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg\/kg), metformin (200 mg\/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1\u03b1) and protein (AMPK, GLUT4, and PPAR-\u03b3) expression in muscle were measured. Catalpol (200 mg\/kg) significantly (p &lt; 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1\u03b1) and protein (AMPK, p-AMPK, PPAR-\u03b3 and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK\/SIRT1\/PGC-1\u03b1\/PPAR-\u03b3 activation in the skeletal muscle of T2DM mice.<\/jats:p>","DOI":"10.3390\/biom10101360","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T02:56:43Z","timestamp":1600916203000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK\/SIRT1\/PGC-1\u03b1\/PPAR-\u03b3 Activation"],"prefix":"10.3390","volume":"10","author":[{"given":"Kah Heng","family":"Yap","sequence":"first","affiliation":[{"name":"School of Postgraduate Studies, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4826-9143","authenticated-orcid":false,"given":"Gan Sook","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuren","family":"Candasamy","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swee Ching","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Postgraduate Studies, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadab","family":"Md","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abu Bakar","family":"Abdul Majeed","sequence":"additional","affiliation":[{"name":"Universiti Teknologi MARA, Sungai Buloh-Selayang Medical-Dental Campus, Jalan Hospital, Sungai Buloh, Selangor 47000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7886-2909","authenticated-orcid":false,"given":"Subrat Kumar","family":"Bhattamisra","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). 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