title: Thioredoxin binding protein-2 inhibits excessive fetal hypoglycemia during maternal starvation by suppressing insulin secretion in mice.
abstract: Glucose is a major fuel for fetal development. Fetal blood glucose level is mainly dependent on maternal blood glucose concentration, though it is also regulated by fetal insulin level. Thioredoxin binding protein-2 (TBP-2), which is identical to vitamin D3 up-regulated protein (VDUP1) and thioredoxin interacting protein (Txnip), was recently reported to be a key transcriptional factor controlling glucose metabolism. Here, we elucidated the functions of TBP-2 in maintaining blood glucose homeostasis during the fetal period. TBP-2(+/-) female mice were mated with TBP-2(+/-) male mice; beginning 16.5-d post coitum, pregnant mice were fed or fasted for 24 h. Under conditions of maternal starvation, the blood glucose levels of TBP-2(-/-) fetuses were significantly lower than those of TBP-2(+/+) fetuses, corresponding to the elevated plasma insulin levels of TBP-2(-/-) fetuses compared with those of TBP-2(+/+) fetuses. There was no difference between TBP-2(+/+) and TBP-2(-/-) fetuses in terms of their pancreatic beta-cell masses or the expression of placental glucose transporters under conditions of either maternal feeding or fasting. Thus, during maternal fasting, fetal TBP-2 suppresses excessive insulin secretion to maintain the fetus's glucose levels, implying that TBP-2 is a critical molecule in mediating fetal glucose homeostasis depending on nutrient availability.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Haruta
authors.initials: H
authors.lastname: Mogami
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yura
authors.forename: Keiji
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujii
authors.forename: Kohei
authors.initials: K
authors.lastname: Fujita
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Kakui
authors.forename: Eiji
authors.initials: E
authors.lastname: Kondoh
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D048070:Fetal Nutrition Disorders / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D020567:Fetal Weight; D005786:Gene Expression Regulation; D005865:Gestational Age; D005943:Gluconeogenesis / Q000235:genetics; D006706:Homeostasis; D007003:Hypoglycemia / Q000097:blood / Q000196:embryology / Q000235:genetics / Q000517:prevention & control*; D007328:Insulin / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000196:embryology / Q000378:metabolism; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D013217:Starvation / Q000097:blood / Q000150:complications* / Q000235:genetics; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; C445672:Txnip protein, mouse; D019344:Lactic Acid; D013879:Thioredoxins