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...

Full description

Saved in:
Bibliographic Details
Published inInternational journal of molecular sciences Vol. 24; no. 20; p. 15464
Main Authors Alshafei, Mohammed, Schulze, Torben, Morsi, Mai, Panten, Uwe, Rustenbeck, Ingo
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.10.2023
MDPI
Subjects
Biosynthesis
cytosolic calcium concentration
Dextrose
Experiments
Fluorescence
Glucose
Insulin
insulin secretion
metabolic amplification
Metabolism
Metabolites
mitochondria
Pancreatic beta cells
pancreatic islets
Proteins
Tolbutamide
Germany
Online AccessGet full text

Cover

More Information
Summary: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 [Ca2+]i 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally to this study.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242015464