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Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice

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Abstract

The maternal deficiency of vitamin D can act on organogenesis in mice offspring, being a risk factor for chronic diseases in adulthood. This study investigates the effects of maternal deficiency of vitamin D on structural islet remodeling and insulin-signaling pathway in the offspring. We studied male C57Bl/6 offspring at 3-month old (n = 10/group) from mother fed one of the two diets: control diet (C) or vitamin D-restricted diet (VitD−). After weaning, offspring only fed the control diet ad libitum. In the offspring, we studied insulin production, islet remodeling, and islet protein expression of the insulin-signaling pathway (Western blotting, isolated islet, n = 5/group). VitD− offspring showed greater glycemia (P = 0.012), smaller beta-cell mass (P = 0.014), and hypoinsulinemia (P = 0.024) than C offspring. Comparing VitD− offspring with C offspring, we observed lower protein levels in islet of insulin (P = 0.003), insulin receptor substrate-1 (P = 0.025), phosphatidylinositol-3-kinases (P = 0.045), 3-phosphoinositide-dependent protein kinase 1 (P = 0.017), protein kinase B (P = 0.028), with reduced expression of pancreas/duodenum homeobox-1 (PDX-1) (P = 0.016), glucose transporter-2 (P = 0.003), and glucokinase (P = 0.045). The maternal vitamin D-restricted diet modifies the development of the pancreas of the offspring, leading to islet remodeling and altered insulin-signaling pathway. The decrease of PDX-1 is probably significant to the changes in the beta-cell mass and insulin secretion in adulthood.

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Abbreviations

1,25(OH)2D3 :

1,25-Dihydroxyvitamin D3

25(OH)D:

25-Hydroxyvitamin D

A[islet]:

Mean cross-sectional area of the islet

AKT:

Protein kinase B

AU:

Arbitrary units

AUC:

Area under the curve

BM:

Body mass

C:

Control diet

CYP27B1:

1-α-Hydroxylase, cytochrome p450 27B1

FoxO1:

Forkhead transcription factor 1

GLK:

Glucokinase

GLUT:

Glucose transporter

IRS-1:

Insulin receptor substrate-1

M[islet]:

Islet mass

OGTT:

Oral glucose tolerance test

pAKT:

Phosphorylated protein kinase B

PDK-1:

3-phosphoinositide-dependent protein kinase 1

pFoxO1:

Phosphorylated forkhead transcription factor 1

PDX-1:

Pancreas/duodenum homeobox-1

PI3-K:

Phosphatidylinositol-3-kinases

Q A[islet]:

Numerical density per area of the islet

VDR:

Vitamin D receptor

VitD− :

Vitamin D-restricted diet

Vv:

Volume density

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Acknowledgments

We thank Thatiany Marinho, Aline Penna, Gezileia Lau, and Michele Soares for the technical assistance.

Funding

This work was supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil) and FAPERJ (Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro of Brazil).

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Authors and Affiliations

  1. Laboratorio de Morfometria, Metabolismo e Doenca Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado de Rio de Janeiro - UERJ, Av. 28 de Setembro, 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil

    Thais C. Maia-Ceciliano, Andre R. C. Barreto-Vianna, Sandra Barbosa-da-Silva, Marcia B. Aguila, Tatiane S. Faria & Carlos A. Mandarim-de-Lacerda

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  1. Thais C. Maia-Ceciliano
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  2. Andre R. C. Barreto-Vianna
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Correspondence to Carlos A. Mandarim-de-Lacerda.

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Maia-Ceciliano, T.C., Barreto-Vianna, A.R.C., Barbosa-da-Silva, S. et al. Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice. Endocrine 54, 60–69 (2016). https://doi.org/10.1007/s12020-016-0973-y

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