title: Expression of Ins1 and Ins2 genes in mouse fetal liver.
abstract: A possible cure for diabetes is explored by using non-pancreatic cells such as fetal hepatocytes. The expression of insulin and transcription factors for insulin is investigated in mouse fetal liver. We detected mRNAs for insulin I (Ins1) and insulin II (Ins2) and proinsulin- and mature insulin-positive cells in mouse fetal liver by reverse transcription plus the polymerase chain reaction and immunohistochemistry. Glucagon, somatostatin and pancreatic polypeptide were not expressed throughout development. Mouse Ins2 and Ins1 promoters were transiently activated in mouse fetal hepatocytes of embryonic days 13.5 and 16.5, respectively. Pancreatic and duodenal homeobox 1 (Pdx1) mRNA was not expressed during development of the liver. In contrast, mRNAs and proteins of neurogenic differentiation (NeuroD)/β cell E-box transactivator 2 (Beta2) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MafA) were almost simultaneously expressed with insulin genes in the liver. Ins2 and Ins1 promoters were activated in hepatoma cells by the transfection of the expression vector for NeuroD/Beta2 alone and by the combination of NeuroD/Beta2 and MafA, respectively. These results indicate that the expression of NeuroD/Beta2 and MafA is linked temporally with the transcription of Ins2 and Ins1 genes in mouse fetal liver and suggest the potential usage of fetal hepatocytes to make insulin-producing β cells by introducing transcription factors.
authors.affiliation: Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Murakami-Kawaguchi
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Onogawa
authors.forename: Koji
authors.initials: K
authors.lastname: Nata
authors.forename: Asako
authors.initials: A
authors.lastname: Itaya-Hironaka
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Sakuramoto-Tsuchida
authors.forename: Akiyo
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Ota
authors.forename: Maiko
authors.initials: M
authors.lastname: Takeda
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005934:Glucagon / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000196:embryology* / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005934:Glucagon; D018398:Homeodomain Proteins; D007328:Insulin; D051473:Maf Transcription Factors, Large; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D013004:Somatostatin; D015534:Trans-Activators; C514817:Ins1 protein, mouse; C561967:Ins2 protein, mouse; C485160:Mafa protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein; C093564:Neurogenic differentiation factor 1