Cargando…
The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes
Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin cl...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814145/ https://www.ncbi.nlm.nih.gov/pubmed/35115614 http://dx.doi.org/10.1038/s41598-022-05704-y |
_version_ | 1784645004823625728 |
---|---|
author | Okura, Tsuyoshi Fujioka, Yohei Nakamura, Risa Kitao, Sonoko Ito, Yuichi Anno, Mari Matsumoto, Kazuhisa Shoji, Kyoko Matsuzawa, Kazuhiko Izawa, Shoichiro Okura, Hiroko Ueta, Etsuko Kato, Masahiko Imamura, Takeshi Taniguchi, Shin-ichi Yamamoto, Kazuhiro |
author_facet | Okura, Tsuyoshi Fujioka, Yohei Nakamura, Risa Kitao, Sonoko Ito, Yuichi Anno, Mari Matsumoto, Kazuhisa Shoji, Kyoko Matsuzawa, Kazuhiko Izawa, Shoichiro Okura, Hiroko Ueta, Etsuko Kato, Masahiko Imamura, Takeshi Taniguchi, Shin-ichi Yamamoto, Kazuhiro |
author_sort | Okura, Tsuyoshi |
collection | PubMed |
description | Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction. |
format | Online Article Text |
id | pubmed-8814145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88141452022-02-07 The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes Okura, Tsuyoshi Fujioka, Yohei Nakamura, Risa Kitao, Sonoko Ito, Yuichi Anno, Mari Matsumoto, Kazuhisa Shoji, Kyoko Matsuzawa, Kazuhiko Izawa, Shoichiro Okura, Hiroko Ueta, Etsuko Kato, Masahiko Imamura, Takeshi Taniguchi, Shin-ichi Yamamoto, Kazuhiro Sci Rep Article Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction. Nature Publishing Group UK 2022-02-03 /pmc/articles/PMC8814145/ /pubmed/35115614 http://dx.doi.org/10.1038/s41598-022-05704-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Okura, Tsuyoshi Fujioka, Yohei Nakamura, Risa Kitao, Sonoko Ito, Yuichi Anno, Mari Matsumoto, Kazuhisa Shoji, Kyoko Matsuzawa, Kazuhiko Izawa, Shoichiro Okura, Hiroko Ueta, Etsuko Kato, Masahiko Imamura, Takeshi Taniguchi, Shin-ichi Yamamoto, Kazuhiro The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes |
title | The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes |
title_full | The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes |
title_fullStr | The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes |
title_full_unstemmed | The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes |
title_short | The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes |
title_sort | sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in japanese patients with type 2 diabetes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814145/ https://www.ncbi.nlm.nih.gov/pubmed/35115614 http://dx.doi.org/10.1038/s41598-022-05704-y |
work_keys_str_mv | AT okuratsuyoshi thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT fujiokayohei thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT nakamurarisa thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT kitaosonoko thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT itoyuichi thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT annomari thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT matsumotokazuhisa thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT shojikyoko thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT matsuzawakazuhiko thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT izawashoichiro thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT okurahiroko thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT uetaetsuko thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT katomasahiko thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT imamuratakeshi thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT taniguchishinichi thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT yamamotokazuhiro thesodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT okuratsuyoshi sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT fujiokayohei sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT nakamurarisa sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT kitaosonoko sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT itoyuichi sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT annomari sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT matsumotokazuhisa sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT shojikyoko sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT matsuzawakazuhiko sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT izawashoichiro sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT okurahiroko sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT uetaetsuko sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT katomasahiko sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT imamuratakeshi sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT taniguchishinichi sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes AT yamamotokazuhiro sodiumglucosecotransporter2inhibitoripragliflozinimprovesliverfunctionandinsulinresistanceinjapanesepatientswithtype2diabetes |