Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons

Li, Ling; Gao, Lin; Wang, Kejia; Ma, Xianhua; Chang, Xusheng; Shi, Jian Hui; Zhang, Ye; Yin, Kai; Liu, Zhimin; Shi, Yuguang; Xie, Zhifang; Zhang, Weiping J.

doi:10.1038/srep20438

Cited by 15 publications

(18 citation statements)

References 42 publications

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“…To our knowledge, this is the first report of insulin production in ChP. Previous work with insulin reporter genetic models demonstrated Ins2 expression in murine ChP (38,39) but no Ins2 promoter activity in any other brain structure. These models, however, failed to detect insulin mRNA or its corresponding protein.…”

Section: Discussionmentioning

confidence: 61%

Release of insulin produced by the choroid plexis is regulated by serotonergic signaling

Mazucanti¹,

Liu²,

Lang³

et al. 2019

JCI Insight

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Section: Discussionmentioning

confidence: 61%

Release of insulin produced by the choroid plexis is regulated by serotonergic signaling

Mazucanti¹,

Liu²,

Lang³

et al. 2019

JCI Insight

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“…To generate b-cell-specific knockout (bKO) mice of Tph1, Htr2b, Prlr, and Stat5, Ins2-Cre (MGI 2387657) mice were mated with mice harboring a Tph1 floxed allele (MGI 6271993), an Htr2b floxed allele (MGI 3837400), a Prlr floxed allele, and a Stat5 floxed allele (MGI 3055318), respectively (9)(10)(11)(12)(13)(14). To generate Ghr bKO mice, Ins2-Cre mice were mated with mice harboring a Ghr floxed allele (MGI 5056123) (15,16). All Cre mice used in this study lacked the GH minigene, which has been shown to induce ectopic 5-HT production (17,18).…”

Section: Animal Experimentsmentioning

confidence: 99%

Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation

Moon

Kim

et al. 2019

Diabetes

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A sufficient b-cell mass is crucial for preventing diabetes, and perinatal b-cell proliferation is important in determining the adult b-cell mass. However, it is not yet known how perinatal b-cell proliferation is regulated. Here, we report that serotonin regulates b-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In b-cell-specific Tph1 knockout (Tph1 bKO) mice, perinatal b-cell proliferation was reduced along with the loss of serotonin production in b-cells. Adult Tph1 bKO mice exhibited glucose intolerance with decreased b-cell mass. Disruption of Htr2b in b-cells also resulted in decreased perinatal b-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in b-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the b-cell mass by regulating perinatal b-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.

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“…3l, n = 10). Since Rip-Cre has been previously implicated in hypothalamus and hippocampus 17 . As shown in supplementary Fig.…”

mentioning

confidence: 99%

Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion

Zhao

Wang

et al. 2020

Nat Commun

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B cell dysfunction due to obesity can be associated with alterations in the levels of micro-RNAs (miRNAs). However, the role of miRNAs in these processes remains elusive. Here, we show that miR-802 is increased in the pancreatic islets of obese mouse models and demonstrate that inducible transgenic overexpression of miR-802 in mice causes impaired insulin transcription and secretion. We identify Foxo1 as a transcription factor of miR-802 promoting its transcription, and NeuroD1 and Fzd5 as targets of miR-802-dependent silencing. Repression of NeuroD1 in β cell and primary islets impairs insulin transcription and reduction of Fzd5 in β cell, which, in turn, impairs Ca 2+ signaling, thereby repressing calcium influx and decreasing insulin secretion. We functionally create a novel network between obesity and β cell dysfunction via miR-802 regulation. Elucidation of the impact of obesity on microRNA expression can broaden our understanding of pathophysiological development of diabetes.

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Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons

Cited by 15 publications

References 42 publications

Release of insulin produced by the choroid plexis is regulated by serotonergic signaling

Release of insulin produced by the choroid plexis is regulated by serotonergic signaling

Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation

Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion

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