Impact of heart-specific disruption of the circadian clock on systemic glucose metabolism in mice
| Autor: | Sabine S. Gouraud, Hue Thi Le, Fuyuki Sato, Zaw Lin Thein, Hidefumi Waki, Masanobu Maeda, Akira Kohsaka, Tsuyoshi Otsuka, Yasuteru Muragaki, Tomomi Nakao, Hayato Ihara, Masako Nakanishi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Glucose medicine.medical_specialty Time Factors Genotype Physiology glucose metabolism Circadian clock heart Carbohydrate metabolism Biology 03 medical and health sciences 0302 clinical medicine Insulin resistance Physiology (medical) Internal medicine medicine Animals Phosphorylation Protein kinase B Cells Cultured Heart Failure Mice Knockout Behavior Animal Myocardium Skeletal muscle ARNTL Transcription Factors medicine.disease Circadian Rhythm CLOCK Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Endocrinology Phenotype Liver Hyperglycemia Insulin Resistance Pancreas Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery |
| DOI: | 10.6084/m9.figshare.5729463.v1 |
| Popis: | The daily rhythm of glucose metabolism is governed by the circadian clock, which consists of cell-autonomous clock machineries residing in nearly every tissue in the body. Disruption of these clock machineries either environmentally or genetically induces the dysregulation of glucose metabolism. Although the roles of clock machineries in the regulation of glucose metabolism have been uncovered in major metabolic tissues, such as the pancreas, liver, and skeletal muscle, it remains unknown whether clock function in non-major metabolic tissues also affects systemic glucose metabolism. Here, we tested the hypothesis that disruption of the clock machinery in the heart might also affect systemic glucose metabolism, because heart function is known to be associated with glucose tolerance. We examined glucose and insulin tolerance as well as heart phenotypes in mice with heart-specific deletion of Bmal1, a core clock gene. Bmal1 deletion in the heart not only decreased heart function but also led to systemic insulin resistance. Moreover, hyperglycemia was induced with age. Furthermore, heart-specific Bmal1-deficient mice exhibited decreased insulin-induced phosphorylation of Akt in the liver, thus indicating that Bmal1 deletion in the heart causes hepatic insulin resistance. Our findings revealed an unexpected effect of the function of clock machinery in a non-major metabolic tissue, the heart, on systemic glucose metabolism in mammals. |
| Databáze: | OpenAIRE |
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