The levels of Pdx1/insulin, Cacna1c and Cacna1d, and β-cell mass in a rat model of intrauterine undernutrition

Abstract

Objective. To elucidate the underlying mechanisms responsible for β-cell mass and function in response to intrauterine growth restriction (IUGR).

Methods. Offspring from undernourished mother rats with birth weight <−2 SD (IUGR group) and from standard-nourished rats with birth weight between mean ±1SD normal birth weight (NBW group) were examined. Levels of fasting glucose, serum insulin, and insulin-like growth factor-1 (IGF-1) were analyzed. Entire pancreas or islet-like cell clusters (ICCs) were collected to evaluate relative β-cell mass and determine the genetic and protein profiles of pancreatic and duodenal homeobox 1 (Pdx1), Cacna1c and Cacna1d using real-time PCR, immunohistochemical staining, and western blotting at day (d) of birth and at d21 of age.

Results. Fasting serum insulin and IGF-1 concentrations were significantly lower in the IUGR group than in the NBW group at d0 and d21. The levels of Pdx1 and insulin mRNAs in IUGR pancreas were also decreased. At birth, the ratios of β-cell mass to body weight were not significantly different between the two groups. However, by d21 the relative β-cell mass in IUGR had not grown to compensate for the increase in body weight, as compared to the NBW group (p < 0.05). The Cacna1c and Cacna1d proteins were significantly higher in the NBW group than that in the IUGR group at birth, but there were no statistical differences at d21.

Conclusion. Decreased Pdx1 levels and IGF-1 concentration restrain β-cell mass and insulin expression in rat offspring from undernourished mothers. However, Cacna1c and Cacna1d expression were able to reach normal levels as the IUGR rats were aged, indicating that these factors were not responsible for the IUGR rat phenotype of insulin resistance and β-cell dysfunction in later life.

Keywords:

• Birth weight
• insulin
• IUGR
• Pdx1

Acknowledgements

The authors thank technician W.-Z. Gu, L.-Q. Chen, Y.-D. Wu for technical assistance. This work was supported by the Natural Science Foundation of Zhejiang Province of China (J20060685) and was also supported by the Natural Science Foundation of China (No 30971125). The authors hereby declare that there is no conflict of interest that would prejudice the impartiality of this scientific work. None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.