{"title":"350-OR: 在胰腺分化过程中,分娩事件调节内分泌的产生","authors":"AGENA SUZUKI, TOMOMI TAGUCHI, SHIORI ITO, HIDEAKI SHIMOTATARA, KAORI KIMURA, NAOYA SHIMIZU, REI FUJISHIMA, MIWA HIMURO, TAKESHI MIYATSUKA","doi":"10.2337/db24-350-or","DOIUrl":null,"url":null,"abstract":"It is essential to decipher developmental features of each endocrine cell, which leads to exploring efficient methods for generating surrogate β cells. We previously developed three reporter mouse lines to quantify the genesis of endocrine progenitor cells, β cells, and α cells. Flow cytometry analysis revealed a significant decrease in the number of newly-generated endocrine progenitors and β cells after birth. Based on these findings, we hypothesized that environmental changes during parturition could affect endocrine genesis. The number of newly-generated endocrine cells was quantified with the reporter mouse lines at the following stages: (i) embryonic day 19.5 (E19.5) embryos, whose parturitions were prolonged by progesterone or COX-1 inhibitor SC-560 vs. newborn pups at postnatal day 0.5 (P0.5) (both were dissected at 19.5 days after coitus), and (ii) premature pups treated with anti-progesterone drug RU-486 (both were at 18.5 days after coitus) vs. E18.5 embryos. Flow cytometry with Neurog3-Timer pancreata demonstrated that the percentage of green-fluorescent progenitors was (i) significantly higher in E19.5 embryos than in P0.5 pups (0.80% vs. 0.22%, p<0.001), and (ii) significantly lower in premature pups than in E18.5 embryos (0.66% vs. 0.93%, p=0.0018). Likewise, flow cytometry with Ins1-Timer pancreata resulted in a significant increase in β-cell genesis at E19.5 than at P0.5 (0.36% vs. 0.16%, p<0.001). Surprisingly, flow cytometry with Gcg-Timer mice resulted in (i) a significant decrease in α-cell genesis at E19.5 than at P0.5 (2.1% vs. 2.4%, p=0.035), and (ii) a significant increase in premature pups 18.5 days after coitus than in E18.5 embryos (0.77% vs. 0.58%, p=0.022), which is in contrast with the findings in Neurog3-Timer and Ins1-Timer pancreata. Thus, parturition events suppress the generation of endocrine progenitors and β cells, but not α-cell genesis, which may reflect distinct molecular mechanisms in α-cell lineage during parturition. Disclosure A. Suzuki: None. T. Taguchi: None. S. Ito: None. H. Shimotatara: None. K. Kimura: None. N. Shimizu: None. R. Fujishima: None. M. Himuro: None. T. Miyatsuka: None.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"350-OR: Parturition Event Regulates Endocrine Genesis during Pancreas Differentiation\",\"authors\":\"AGENA SUZUKI, TOMOMI TAGUCHI, SHIORI ITO, HIDEAKI SHIMOTATARA, KAORI KIMURA, NAOYA SHIMIZU, REI FUJISHIMA, MIWA HIMURO, TAKESHI MIYATSUKA\",\"doi\":\"10.2337/db24-350-or\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"It is essential to decipher developmental features of each endocrine cell, which leads to exploring efficient methods for generating surrogate β cells. We previously developed three reporter mouse lines to quantify the genesis of endocrine progenitor cells, β cells, and α cells. Flow cytometry analysis revealed a significant decrease in the number of newly-generated endocrine progenitors and β cells after birth. Based on these findings, we hypothesized that environmental changes during parturition could affect endocrine genesis. The number of newly-generated endocrine cells was quantified with the reporter mouse lines at the following stages: (i) embryonic day 19.5 (E19.5) embryos, whose parturitions were prolonged by progesterone or COX-1 inhibitor SC-560 vs. newborn pups at postnatal day 0.5 (P0.5) (both were dissected at 19.5 days after coitus), and (ii) premature pups treated with anti-progesterone drug RU-486 (both were at 18.5 days after coitus) vs. E18.5 embryos. Flow cytometry with Neurog3-Timer pancreata demonstrated that the percentage of green-fluorescent progenitors was (i) significantly higher in E19.5 embryos than in P0.5 pups (0.80% vs. 0.22%, p<0.001), and (ii) significantly lower in premature pups than in E18.5 embryos (0.66% vs. 0.93%, p=0.0018). Likewise, flow cytometry with Ins1-Timer pancreata resulted in a significant increase in β-cell genesis at E19.5 than at P0.5 (0.36% vs. 0.16%, p<0.001). Surprisingly, flow cytometry with Gcg-Timer mice resulted in (i) a significant decrease in α-cell genesis at E19.5 than at P0.5 (2.1% vs. 2.4%, p=0.035), and (ii) a significant increase in premature pups 18.5 days after coitus than in E18.5 embryos (0.77% vs. 0.58%, p=0.022), which is in contrast with the findings in Neurog3-Timer and Ins1-Timer pancreata. Thus, parturition events suppress the generation of endocrine progenitors and β cells, but not α-cell genesis, which may reflect distinct molecular mechanisms in α-cell lineage during parturition. Disclosure A. Suzuki: None. T. Taguchi: None. S. Ito: None. H. Shimotatara: None. K. Kimura: None. N. Shimizu: None. R. Fujishima: None. M. Himuro: None. T. Miyatsuka: None.\",\"PeriodicalId\":11376,\"journal\":{\"name\":\"Diabetes\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-07-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2337/db24-350-or\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/db24-350-or","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
350-OR: Parturition Event Regulates Endocrine Genesis during Pancreas Differentiation
It is essential to decipher developmental features of each endocrine cell, which leads to exploring efficient methods for generating surrogate β cells. We previously developed three reporter mouse lines to quantify the genesis of endocrine progenitor cells, β cells, and α cells. Flow cytometry analysis revealed a significant decrease in the number of newly-generated endocrine progenitors and β cells after birth. Based on these findings, we hypothesized that environmental changes during parturition could affect endocrine genesis. The number of newly-generated endocrine cells was quantified with the reporter mouse lines at the following stages: (i) embryonic day 19.5 (E19.5) embryos, whose parturitions were prolonged by progesterone or COX-1 inhibitor SC-560 vs. newborn pups at postnatal day 0.5 (P0.5) (both were dissected at 19.5 days after coitus), and (ii) premature pups treated with anti-progesterone drug RU-486 (both were at 18.5 days after coitus) vs. E18.5 embryos. Flow cytometry with Neurog3-Timer pancreata demonstrated that the percentage of green-fluorescent progenitors was (i) significantly higher in E19.5 embryos than in P0.5 pups (0.80% vs. 0.22%, p<0.001), and (ii) significantly lower in premature pups than in E18.5 embryos (0.66% vs. 0.93%, p=0.0018). Likewise, flow cytometry with Ins1-Timer pancreata resulted in a significant increase in β-cell genesis at E19.5 than at P0.5 (0.36% vs. 0.16%, p<0.001). Surprisingly, flow cytometry with Gcg-Timer mice resulted in (i) a significant decrease in α-cell genesis at E19.5 than at P0.5 (2.1% vs. 2.4%, p=0.035), and (ii) a significant increase in premature pups 18.5 days after coitus than in E18.5 embryos (0.77% vs. 0.58%, p=0.022), which is in contrast with the findings in Neurog3-Timer and Ins1-Timer pancreata. Thus, parturition events suppress the generation of endocrine progenitors and β cells, but not α-cell genesis, which may reflect distinct molecular mechanisms in α-cell lineage during parturition. Disclosure A. Suzuki: None. T. Taguchi: None. S. Ito: None. H. Shimotatara: None. K. Kimura: None. N. Shimizu: None. R. Fujishima: None. M. Himuro: None. T. Miyatsuka: None.
期刊介绍:
Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes.
However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.