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

doi:10.1038/s12276-022-00797-x

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 KimKyu Sang Park, Hyun Jin Kim, Minho Shong

Physiology

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Genetic variations in mitoribosomal subunits and mitochondrial transcription factors are related to type 2 diabetes. 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. Crif1^beta+/− 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, Crif1^beta+/− mice showed earlier islet failure in response to high-fat feeding, which was exacerbated by aging. Haploinsufficiency of a single mitoribosomal gene predisposes rodents to glucose intolerance, which resembles the early stages of type 2 diabetes in humans.

Original language	English
Pages (from-to)	932-945
Number of pages	14
Journal	Experimental and Molecular Medicine
Volume	54
Issue number	7
DOIs	https://doi.org/10.1038/s12276-022-00797-x
Publication status	Published - 2022 Jul

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s12276-022-00797-x

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Hong, H. J., Joung, K. H., Kim, Y. K., Choi, M. J., Kang, S. G., Kim, J. T., Kang, Y. E., Chang, J. Y., Moon, J. H., Jun, S., Ro, H. J., Lee, Y., Kim, H., Park, J. H., Kang, B. E., Jo, Y., Choi, H., Ryu, D., Lee, C. H., ... Shong, M. (2022). Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure. Experimental and Molecular Medicine, 54(7), 932-945. https://doi.org/10.1038/s12276-022-00797-x

@article{74ffc41910b74860b18f86ea8ae2354f,

title = "Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure",

abstract = "Genetic variations in mitoribosomal subunits and mitochondrial transcription factors are related to type 2 diabetes. 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. Haploinsufficiency of a single mitoribosomal gene predisposes rodents to glucose intolerance, which resembles the early stages of type 2 diabetes in humans.",

author = "Hong, {Hyun Jung} and Joung, {Kyong Hye} and Kim, {Yong Kyung} and Choi, {Min Jeong} and Kang, {Seul Gi} and Kim, {Jung Tae} and Kang, {Yea Eun} and Chang, {Joon Young} and Moon, {Joon Ho} and Sangmi Jun and Ro, {Hyun Joo} and Yujeong Lee and Hyeongseok Kim and Park, {Jae Hyung} and Kang, {Baeki E.} and Yunju Jo and Heejung Choi and Dongryeol Ryu and Lee, {Chul Ho} and Hail Kim and Park, {Kyu Sang} and Kim, {Hyun Jin} and Minho Shong",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jul,

doi = "10.1038/s12276-022-00797-x",

language = "English",

volume = "54",

pages = "932--945",

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Hong, HJ, Joung, KH, Kim, YK, Choi, MJ, Kang, SG, Kim, JT, Kang, YE, Chang, JY, Moon, JH, Jun, S, Ro, HJ, Lee, Y, Kim, H, Park, JH, Kang, BE, Jo, Y, Choi, H, Ryu, D, Lee, CH, Kim, H, Park, KS, Kim, HJ & Shong, M 2022, 'Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure', Experimental and Molecular Medicine, vol. 54, no. 7, pp. 932-945. https://doi.org/10.1038/s12276-022-00797-x

TY - JOUR

T1 - Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure

AU - Hong, Hyun Jung

AU - Joung, Kyong Hye

AU - Kim, Yong Kyung

AU - Choi, Min Jeong

AU - Kang, Seul Gi

AU - Kim, Jung Tae

AU - Kang, Yea Eun

AU - Chang, Joon Young

AU - Moon, Joon Ho

AU - Jun, Sangmi

AU - Ro, Hyun Joo

AU - Lee, Yujeong

AU - Kim, Hyeongseok

AU - Park, Jae Hyung

AU - Kang, Baeki E.

AU - Jo, Yunju

AU - Choi, Heejung

AU - Ryu, Dongryeol

AU - Lee, Chul Ho

AU - Kim, Hail

AU - Park, Kyu Sang

AU - Kim, Hyun Jin

AU - Shong, Minho

PY - 2022/7

Y1 - 2022/7

N2 - Genetic variations in mitoribosomal subunits and mitochondrial transcription factors are related to type 2 diabetes. 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. Haploinsufficiency of a single mitoribosomal gene predisposes rodents to glucose intolerance, which resembles the early stages of type 2 diabetes in humans.

AB - Genetic variations in mitoribosomal subunits and mitochondrial transcription factors are related to type 2 diabetes. 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. Haploinsufficiency of a single mitoribosomal gene predisposes rodents to glucose intolerance, which resembles the early stages of type 2 diabetes in humans.

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Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure

Abstract

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