Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation
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 resp...
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MDPI AG
2020-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/10/1360 |
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| author | Kah Heng Yap Gan Sook Yee Mayuren Candasamy Swee Ching Tan Shadab Md Abu Bakar Abdul Majeed Subrat Kumar Bhattamisra |
| author_facet | Kah Heng Yap Gan Sook Yee Mayuren Candasamy Swee Ching Tan Shadab Md Abu Bakar Abdul Majeed Subrat Kumar Bhattamisra |
| author_sort | Kah Heng Yap |
| collection | DOAJ |
| description | 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-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (<i>p</i> < 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-1α) and protein (AMPK, p-AMPK, PPAR-γ 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-1α/PPAR-γ activation in the skeletal muscle of T2DM mice. |
| first_indexed | 2024-03-10T16:05:40Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T16:05:40Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-66da63165de043dea84a7ddb637388582023-11-20T14:53:01ZengMDPI AGBiomolecules2218-273X2020-09-011010136010.3390/biom10101360Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ ActivationKah Heng Yap0Gan Sook Yee1Mayuren Candasamy2Swee Ching Tan3Shadab Md4Abu Bakar Abdul Majeed5Subrat Kumar Bhattamisra6School of Postgraduate Studies, International Medical University, Bukit Jalil, Kuala Lumpur 57000, MalaysiaDepartment of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, MalaysiaDepartment of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, MalaysiaSchool of Postgraduate Studies, International Medical University, Bukit Jalil, Kuala Lumpur 57000, MalaysiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaUniversiti Teknologi MARA, Sungai Buloh-Selayang Medical-Dental Campus, Jalan Hospital, Sungai Buloh, Selangor 47000, MalaysiaDepartment of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, MalaysiaCatalpol 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-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (<i>p</i> < 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-1α) and protein (AMPK, p-AMPK, PPAR-γ 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-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.https://www.mdpi.com/2218-273X/10/10/1360catalpoltype-2 diabetes mellitusinsulin sensitivityglucose homeostasisoxygen consumption ratemitochondrial respiration |
| spellingShingle | Kah Heng Yap Gan Sook Yee Mayuren Candasamy Swee Ching Tan Shadab Md Abu Bakar Abdul Majeed Subrat Kumar Bhattamisra Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation Biomolecules catalpol type-2 diabetes mellitus insulin sensitivity glucose homeostasis oxygen consumption rate mitochondrial respiration |
| title | Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation |
| title_full | Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation |
| title_fullStr | Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation |
| title_full_unstemmed | Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation |
| title_short | Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation |
| title_sort | catalpol ameliorates insulin sensitivity and mitochondrial respiration in skeletal muscle of type 2 diabetic mice through insulin signaling pathway and ampk sirt1 pgc 1α ppar γ activation |
| topic | catalpol type-2 diabetes mellitus insulin sensitivity glucose homeostasis oxygen consumption rate mitochondrial respiration |
| url | https://www.mdpi.com/2218-273X/10/10/1360 |
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