Summary of ssbd-repos-000424

Name
URL
DOI

Title
Immunostaining and electron microscopy images of tissues and cells
Description

mitochondrial quality control, diabetes, liver, skeletal muscle, pancreas

Submited Date
2025-03-06
Release Date
2025-03-06
Updated Date
-
License
Funding information
-
File formats
Tiff
Data size
118.1 MB

Organism
Mus musculus, Rattus norvegicus, Homo sapiens
Strain
C57BL/6J mice, Sprague–Dawley rat
Cell Line
HepG2
Genes
-
Proteins
-

GO Molecular Function (MF)
-
GO Biological Process (BP)
-
GO Cellular Component (CC)
-
Study Type
-
Imaging Methods
-

Method Summary

See details in Kato, et. al. (2024) Br J Pharmacol.

Related paper(s)

Yuri Kato, Kohei Ariyoshi, Yasunobu Nohara, Naoya Matsunaga, Tsukasa Shimauchi, Naoya Shindo, Akiyuki Nishimura, Xinya Mi, Sang Geon Kim, Tomomi Ide, Eiji Kawanishi, Akio Ojida, Naoki Nakashima, Yasuo Mori, Motohiro Nishida (2024) Inhibition of dynamin-related protein 1-filamin interaction improves systemic glucose metabolism., British journal of pharmacology

Published in 2024 Jul 10 (Electronic publication in July 10, 2024, midnight )

(Abstract) 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.

Contact(s)
Motohiro Nishida, Yuri Kato
Organization(s)
Kyushu University, National Institutes of Natural Sciences , Graduate School of Pharmaceutical Sciences, National Institute for Physiological Sciences & Exploratory Research Center on Life and Living Systems , Department of Physiology,Division of Cardiocirculatory Signaling
Image Data Contributors
Quantitative Data Contributors

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