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pmid:35804190
Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure.
Hyun Jung Hong · Kyong Hye Joung · Yong Kyung Kim · Min Jeong Choi · Seul Gi Kang · Jung Tae Kim · Yea Eun Kang · Joon Young Chang · Joon Ho Moon · Sangmi Jun · Hyun-Joo Ro · Yujeong Lee · Hyeongseok Kim · Jae-Hyung Park · Baeki E Kang · Yunju Jo · Heejung Choi · Dongryeol Ryu · Chul-Ho Lee · Hail Kim · Kyu-Sang Park · Hyun Jin Kim · Minho Shong
Experimental & molecular medicine · 2022 doi:10.1038/s12276-022-00797-x
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Complete file
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However, the role of islet mitoribosomes in the development of type 2 diabetes has not been determined. We investigated the effects of the mitoribosomal gene on β-cell function and glucose homeostasis. Mitoribosomal gene expression was analyzed in datasets from the NCBI GEO website (GSE25724, GSE76894, and GSE76895) and the European Nucleotide Archive (ERP017126), which contain the transcriptomes of type 2 diabetic and nondiabetic organ donors. We found deregulation of most mitoribosomal genes in islets from individuals with type 2 diabetes, including partial downregulation of CRIF1. The phenotypes of haploinsufficiency in a single mitoribosomal gene were examined using β-cell-specific Crif1 (Mrpl59) heterozygous-deficient mice. Crif1beta+/- mice had normal glucose tolerance, but their islets showed a loss of first-phase glucose-stimulated insulin secretion. They also showed increased β-cell mass associated with higher expression of Reg family genes. However, Crif1beta+/- mice showed earlier islet failure in response to high-fat feeding, which was exacerbated by aging. 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