Inhibition of dynamin-related protein 1-filamin interaction improves systemic glucose metabolism.

التفاصيل البيبلوغرافية
العنوان:	Inhibition of dynamin-related protein 1-filamin interaction improves systemic glucose metabolism.
المؤلفون:	Kato Y; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Ariyoshi K; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Nohara Y; Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto, Japan., Matsunaga N; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Shimauchi T; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.; Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.; National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.; Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Aichi, Japan., Shindo N; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Nishimura A; National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.; Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.; SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi, Japan., Mi X; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Kim SG; College of Pharmacy, Dongguk University-Seoul, Goyang-si, South Korea., Ide T; Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Kawanishi E; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Ojida A; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Nakashima N; Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Mori Y; Graduate School of Engineering, Kyoto University, Kyoto, Japan., Nishida M; Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.; National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.; Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.; SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi, Japan.
المصدر:	British journal of pharmacology [Br J Pharmacol] 2024 Jul 10. Date of Electronic Publication: 2024 Jul 10.
Publication Model:	Ahead of Print
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE
أسماء مطبوعة:	Publication: London : Wiley Original Publication: London, Macmillian Journals Ltd.
مستخلص:	Background and Purpose: Maintaining mitochondrial quality is attracting attention as a new strategy to treat diabetes and diabetic complications. We previously reported that mitochondrial hyperfission by forming a protein complex between dynamin-related protein (Drp) 1 and filamin, mediates chronic heart failure and cilnidipine, initially developed as an L/N-type Ca ²⁺ channel blocker, improves heart failure by inhibiting Drp1-filamin protein complex. We investigated whether cilnidipine improves hyperglycaemia of various diabetic mice models. Experimental Approach: Retrospective analysis focusing on haemoglobin A1c (HbA1c) was performed in hypertensive and hyperglycaemic patients taking cilnidipine and amlodipine. After developing diabetic mice by streptozotocin (STZ) treatment, an osmotic pump including drug was implanted intraperitoneally, followed by weekly measurements of blood glucose levels. Mitochondrial morphology was analysed by electron microscopy. A Ca ²⁺ channel-insensitive cilnidipine derivative (1,4-dihydropyridine [DHP]) was synthesized and its pharmacological effect was evaluated using obese (ob/ob) mice fed with high-fat diet (HFD). Key Results: In patients, cilnidipine was superior to amlodipine in HbA1c lowering effect. Cilnidipine treatment improved systemic hyperglycaemia and mitochondrial morphological abnormalities in STZ-exposed mice, without lowering blood pressure. Cilnidipine failed to improve hyperglycaemia of ob/ob mice, with suppressing insulin secretion. 1,4-DHP improved hyperglycaemia and mitochondria abnormality in ob/ob mice fed HFD. 1,4-DHP and cilnidipine improved basal oxygen consumption rate of HepG2 cells cultured under 25 mM glucose. Conclusion and Implications: Inhibition of Drp1-filamin protein complex formation becomes a new strategy for type 2 diabetes treatment. (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
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معلومات مُعتمدة:	22H02772 Japan Society for the Promotion of Science; 22K19395 Japan Society for the Promotion of Science; 23K06164 Japan Society for the Promotion of Science; JPMJCR2024 Japan Science and Technology Corporation; 21H05269 Grant-in-Aid for Scientific Research on Innovative Areas (A); 21H05258 Grant-in-Aid for Scientific Research on Innovative Areas (A); JP23ama121031 Japan Agency for Medical Research and Development; 23-318 Joint Research of the Exploratory Research Center on Life and Living Systems (ExCELLS); 2017K1A1A2004511 National Research Foundation of Korea (NRF) funded by the Korean government (MSIP); Naito Foundation
فهرسة مساهمة:	Keywords: Drp1; filamin; insulin; mitochondria quality control; type2 diabetes
تواريخ الأحداث:	Date Created: 20240710 Latest Revision: 20240710
رمز التحديث:	20240711
DOI:	10.1111/bph.16487
PMID:	38986570
قاعدة البيانات:	MEDLINE

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