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There is a widespread interest in defining factors and mechanisms that stimulate proliferation of pancreatic islet β-cells. Pregnancy is a special period when the pancreatic islet displays a highly reproducible physiological proliferation. However, the molecular mechanism of β-cell proliferation during pregnancy is unclear. Here, we used cDNA expression array to explore gene expression profiles of islet at various stages of pregnancy in rats. Differentially expressed genes related to islet proliferation were screened by bioinformatics methods, and further verified by real-time PCR, RT-PCR, and Western blotting. Compared with control group, expressions of hundreds of genes were changed during pregnancy. The differentially expressed genes related to islet proliferation were mainly distributed in three groups: genes involved in transcription regulator activity, genes involved in apoptosis or tumor, and genes for Wnt signaling pathway. Among these genes, expressions of Nupr1, Atf3, Btg2, β-catenin, and c-Myc mRNA were up-regulated during pregnancy. A prominent expression of Nupr1 and Atf3 protein was observed in islets on day 10.5 of pregnancy, i.e., with earlier time phases than proliferation peak. Moreover, we found that prolactin (PRL) can increase the proliferation of β-cell in vitro, which is accompanied by up-regulation of Atf3 and Nupr1, indicating that they may play a crucial role in PRL-induced pancreatic β-cell growth. In conclusion, our results suggest that the transcription factor Nupr1, Atf3, and Wnt pathway may play an important role in adaptive proliferation of pancreatic islets during pregnancy in rats.

During pregnancy, the pancreatic islets undergo major structural and functional changes in response to increased peripheral resistance to insulin. In this study, we investigated the adaptive changes of the pancreatic islet beta-cell mass during pregnancy in rats, and explored profiles of islet gene expression at various stages of pregnancy. Some differentially expressed genes were verified by RT-PCR and Real-time PCR. Our results showed that compared with the non-pregnant control group, insulin synthesis, glucose-stimulated insulin secretion, islet beta-cell proliferation, and islet size were all increased in pregnant rats. The study also demonstrated that expression of several-hundred islet genes were changed during pregnancy, especially at day 14.5. The differentially expressed genes identified were distributed into eight main categories according to their biological functions: (1) genes involved in apoptosis or tumor; (2) genes related to binding; (3) genes involved in metabolism; (4) genes related to cell cycle; (5) genes for signal transducer activity; (6) genes related to structural molecule activity; (7) genes involved in transcription regulator activity; (8) genes for transporter activity. Among these genes, regenerating islet-derived 3 alpha (Reg3a) was remarkably increased during pregnancy. We hypothesize that differentially expressed genes may play an important role in adaptation of pancreatic islets during pregnancy in rats. In addition, the markedly increased expression of gene Reg3a is probably related to islet regeneration.

The relationship between subclinical thyroid dysfunction and blood pressure has been controversial and received unsufficient attention. Thus, we performed a cross-sectional study conducted among 6,992 inhabitants from six districts of Jiangsu Province to investigate the association of subclinical thyroid dysfunction with blood pressure in China. The data from 6,583 subjects (4,115 women and 2,468 men) were included and divided into three groups: euthyroidism (n = 5669, 86.11%), subclinical hyperthyroidism (n = 108, 1.65%), and subclinical hypothyroidism (n = 806, 12.24%). In the groups with subclinical hypothyroidism and hyperthyroidism, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were not significantly different from those in the groups with euthyroidism after being adjusted for age, sex, BMI, and smoking status (P0.05). More extensively, the SBP and DBP in the group of subclinical hypothyroidism with lower level of TSH (TSH 4.51-10.00 mIU/l, SCH(1)) were significantly higher than those of participants with euthyroidism (P0.05). Multivariable logistic analysis revealed that subclinical hypothyroidism with lower TSH (TSH 4.51-10.00 mIU/l) was an independent risk factor for increased SBP (OR = 1.28, 95% CI 1.03-1.59, P = 0.028). Similar results could not be found between groups of euthyroid and subclinical hypothyroid with higher level of TSH (TSH10 mIU/l, SCH(2)). Further subdivision of the euthyroid group on the basis of a TSH cut-off of 2.5 mIU/l, revealed still no significant difference in blood pressure after adjustment regardless of whether the TSH levels were in the lower reference (TSH 0.40-2.50 mIU/l, n = 4093) or in the upper reference ranges (TSH 2.51-4.50 mIU/l, n = 1576) (P0.05). We concluded that subclinical thyroid dysfunction was not associated with blood pressure. Neither subclinical hyperthyroidism nor subclinical hypothyroidism independently predicted increased blood pressure.