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Diabetology International

, Volume 5, Issue 1, pp 43–52 | Cite as

Contribution of insulin signaling to the regulation of pancreatic beta-cell mass during the catch-up growth period in a low birth weight mouse model

  • Yuri Yoshida
  • Megumi Fuchita
  • Maki Kimura-Koyanagi
  • Ayumi Kanno
  • Tomokazu Matsuda
  • Shun-ichiro Asahara
  • Naoko Hashimoto
  • Takayuki Isagawa
  • Wataru Ogawa
  • Hiroyuki Aburatani
  • Tetsuo Noda
  • Susumu Seino
  • Masato Kasuga
  • Yoshiaki KidoEmail author
Original Article

Abstract

Children born with low birth weight have a high risk of developing type 2 diabetes mellitus later in life. In this study, we developed a mouse model for low birth weight induced by maternal caloric restriction and investigated its effects on pancreatic β-cells. At birth, the pancreatic β-cell mass in the restricted diet group (RG) offspring was significantly lower than in the control group (CG) offspring. At 8 weeks of age, the pancreatic β-cell mass was greater in the RG offspring than in the CG offspring. RG offspring showed upregulated expression of insulin receptor substrate 2 in islets at 10 weeks of age. Moreover, the activity of insulin signaling molecules in the pancreatic β-cell mass was increased during the period of catch-up growth during the early stage of life. To investigate the effect of insulin signaling on the regulation of pancreatic β-cell mass, we generated β-cell-specific 3-phosphoinositide-dependent protein kinase 1 (PDK1) heterozygous knockout (βPDK1+/−) mice. We detected delayed catch-up growth in the β-cell mass of βPDK1+/− mice that were undernourished as fetuses. Moreover, the insulin signaling pathway was impaired in the islets of βPDK1+/− mice exposed to fetal undernutrition. These findings indicate that fetal undernutrition affects the regulation of pancreatic β-cell mass through altered insulin signaling.

Keywords

Insulin signaling Pancreatic beta-cell Catch-up growth Fetal undernutrition 

Notes

Acknowledgments

We thank M. Nagano and H. Meguro for technical assistance. This work was supported by a grant for CLUSTER from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, to M. Kasuga, a Grant-in-Aid for Creative Scientific Research from MEXT to M. Kasuga (18GS0317), a Grant-in-Aid for Scientific Research from MEXT to Y. Kido (22590981), a Grant-in-Aid for Young Scientists from MEXT to N. Hashimoto (22790863), a Grant from Yamaguchi Endocrine Research Association to N. Hashimoto, and a Danon Institute of Japan Foundation Research Grant to M. Kimura-Koyanagi.

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© The Japan Diabetes Society 2013

Authors and Affiliations

  • Yuri Yoshida
    • 1
  • Megumi Fuchita
    • 1
  • Maki Kimura-Koyanagi
    • 2
  • Ayumi Kanno
    • 2
  • Tomokazu Matsuda
    • 2
  • Shun-ichiro Asahara
    • 2
  • Naoko Hashimoto
    • 2
  • Takayuki Isagawa
    • 4
    • 5
  • Wataru Ogawa
    • 2
  • Hiroyuki Aburatani
    • 5
  • Tetsuo Noda
    • 6
  • Susumu Seino
    • 2
    • 3
  • Masato Kasuga
    • 7
  • Yoshiaki Kido
    • 1
    • 2
    Email author
  1. 1.Division of Medical Chemistry, Department of BiophysicsKobe University Graduate of Health SciencesKobeJapan
  2. 2.Division of Diabetes and Endocrinology, Department of Internal MedicineKobe University Graduate School of MedicineKobeJapan
  3. 3.Division of Cellular and Molecular Medicine, Department of Physiology and Cell BiologyKobe University Graduate School of MedicineKobeJapan
  4. 4.Department of Cardiovascular Medicine, Graduate School of MedicineThe University of TokyoTokyoJapan
  5. 5.Genome Science Division, Research Center for Advanced Science and TechnologyThe University of TokyoTokyoJapan
  6. 6.Department of Cell Biology, Cancer InstituteJapanese Foundation of Cancer ResearchTokyoJapan
  7. 7.National Center for Global Health and MedicineTokyoJapan

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