Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice
Since glucose stimulates protein biosynthesis in beta cells concomitantly with the stimulation of insulin release, the possible interaction of both processes was explored. The protein biosynthesis was inhibited by 10 μM cycloheximide (CHX) 60 min prior to the stimulation of perifused, freshly isolat...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/20/15464 |
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| author | Mohammed Alshafei Torben Schulze Mai Morsi Uwe Panten Ingo Rustenbeck |
| author_facet | Mohammed Alshafei Torben Schulze Mai Morsi Uwe Panten Ingo Rustenbeck |
| author_sort | Mohammed Alshafei |
| collection | DOAJ |
| description | Since glucose stimulates protein biosynthesis in beta cells concomitantly with the stimulation of insulin release, the possible interaction of both processes was explored. The protein biosynthesis was inhibited by 10 μM cycloheximide (CHX) 60 min prior to the stimulation of perifused, freshly isolated or 22 h-cultured NMRI mouse islets. CHX reduced the insulinotropic effect of 25 mM glucose or 500 μM tolbutamide in fresh but not in cultured islets. In cultured islets the second phase of glucose stimulation was even enhanced. In fresh and in cultured islets CHX strongly reduced the content of proinsulin, but not of insulin, and moderately diminished the [Ca<sup>2+</sup>]<sub>i</sub> increase during stimulation. The oxygen consumption rate (OCR) of fresh islets was about 50% higher than that of cultured islets at basal glucose and was significantly increased by glucose but not tolbutamide. In fresh, but not in cultured, islets CHX diminished the glucose-induced OCR increase and changes in the NAD(P)H- and FAD-autofluorescence. It is concluded that short-term CHX exposure interferes with the signal function of the mitochondria, which have different working conditions in fresh and in cultured islets. The interference may not be an off-target effect but may result from the inhibited cytosolic synthesis of mitochondrial proteins. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:12:07Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bfb4561052fd4e878009ea8b301afd102023-11-19T16:47:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201546410.3390/ijms242015464Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female MiceMohammed Alshafei0Torben Schulze1Mai Morsi2Uwe Panten3Ingo Rustenbeck4Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, D38106 Braunschweig, GermanyInstitute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, D38106 Braunschweig, GermanyInstitute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, D38106 Braunschweig, GermanyInstitute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, D38106 Braunschweig, GermanyInstitute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, D38106 Braunschweig, GermanySince glucose stimulates protein biosynthesis in beta cells concomitantly with the stimulation of insulin release, the possible interaction of both processes was explored. The protein biosynthesis was inhibited by 10 μM cycloheximide (CHX) 60 min prior to the stimulation of perifused, freshly isolated or 22 h-cultured NMRI mouse islets. CHX reduced the insulinotropic effect of 25 mM glucose or 500 μM tolbutamide in fresh but not in cultured islets. In cultured islets the second phase of glucose stimulation was even enhanced. In fresh and in cultured islets CHX strongly reduced the content of proinsulin, but not of insulin, and moderately diminished the [Ca<sup>2+</sup>]<sub>i</sub> increase during stimulation. The oxygen consumption rate (OCR) of fresh islets was about 50% higher than that of cultured islets at basal glucose and was significantly increased by glucose but not tolbutamide. In fresh, but not in cultured, islets CHX diminished the glucose-induced OCR increase and changes in the NAD(P)H- and FAD-autofluorescence. It is concluded that short-term CHX exposure interferes with the signal function of the mitochondria, which have different working conditions in fresh and in cultured islets. The interference may not be an off-target effect but may result from the inhibited cytosolic synthesis of mitochondrial proteins.https://www.mdpi.com/1422-0067/24/20/15464cytosolic calcium concentrationinsulin secretionmetabolic amplificationmitochondriapancreatic islets |
| spellingShingle | Mohammed Alshafei Torben Schulze Mai Morsi Uwe Panten Ingo Rustenbeck Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice International Journal of Molecular Sciences cytosolic calcium concentration insulin secretion metabolic amplification mitochondria pancreatic islets |
| title | Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice |
| title_full | Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice |
| title_fullStr | Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice |
| title_full_unstemmed | Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice |
| title_short | Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice |
| title_sort | short term inhibition of translation by cycloheximide concurrently affects mitochondrial function and insulin secretion in islets from female mice |
| topic | cytosolic calcium concentration insulin secretion metabolic amplification mitochondria pancreatic islets |
| url | https://www.mdpi.com/1422-0067/24/20/15464 |
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