MATERNAL DIABETES INDUCES UPREGULATION OF HEPATIC INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1 MRNA EXPRESSION, GROWTH RETARDATION AND DEVELOPMENTAL DELAY AT THE SAME STAGE OF RAT FETAL DEVELOPMENT

1997 ◽  
Vol 152 (1) ◽  
pp. R1-R6 ◽  
Author(s):  
Veeraramani S. Rajaratnam ◽  
Peggy J. Webb ◽  
Renata B. Fishman ◽  
Randal D. Streck

ABSTRACT Since maternal diabetes is associated with fetal growth abnormalities in humans and rats, effects of maternal diabetes on fetal expression of genes regulating growth are of interest. Increased expression of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) is associated with several examples of growth retardation and is upregulated in response to diabetes. As we have shown previously, IGFBP-1 expression is upregulated in gestational day (GD) 14 rat fetuses in response to maternal diabetes. Here we analyze the effect of streptozotocin-induced maternal diabetes on IGFBP-1 mRNA expression during GD12-16 of rat fetal development, using in situ hybridization. IGFBP-1 mRNA was more abundant in GD12-14 fetal livers from diabetic dams than in livers of age-matched controls. This upregulation is not due to the approximately 1-day fetal developmental delay associated with maternal diabetes, as there is no gross difference in the level of IGFBP-1 mRNA in GD13 vs GD12 or GD14 vs GD13 control fetal livers. At GD15-16, however, we detected little difference in IGFBP-1 expression between experimental and control fetuses. This transient period of maternal diabetes-stimulated IGFBP-1 mRNA expression (GD12-14) is coincident with the sensitive period for maternal diabetes-induced defects in fetal growth and development, suggesting that IGFBP-1 is involved in the regulation of fetal growth and development in response to the maternal condition.

1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Ruoyi Zheng ◽  
Wenming Chen ◽  
Weiting Xia ◽  
Jingyu Zheng ◽  
Qing Zhou

Purpose. To assess the expression of insulin-like growth factor binding protein (IGFBP) family and its prognostic impact in ovarian cancer (OC) patients. Materials and Methods. The mRNA expression and protein expression of individual IGFBPs in healthy ovarian samples and OC tissues were explored through Oncomine, Gene Expression Profiling Interactive Analysis, and Human Protein Atlas database. Additionally, the prognostic values of the six IGFBP members in patients with OC were evaluated by Kaplan-Meier plotter. Results. IGFBP2 and IGFBP4 mRNA expression were remarkably upregulated in patients with OC. To be specific, the mRNA expression of IGFBP2 was upregulated in patients with serous ovarian cancer (SOC), while IGFBP1/3/4/5/6 mRNA levels were downregulated. In addition, the IGFBP4 protein expression was upregulated in SOC, and the IGFBP6 protein expression was upregulated in both of SOC and endometrioid ovarian cancer (EOC) tissues. High IGFBP1 mRNA levels showed favorable overall survival (OS) and progression-free survival (PFS) in all OC. Meanwhile, increased IGFBP5/6 mRNA levels revealed worsen OS and PFS in all OC patients. IGFBP4/6 mRNA levels predicted unfavorable OS and PFS only in SOC patients. Moreover, the aberrant mRNA expression of IGFBP1/2/4/5/6 was correlated with significantly prognosis in patients receiving different chemotherapeutic regimens. Conclusion. This study indicates that the IGFBP family reveals distinct prognosis in patients with OC. IGFBP1/2/4/5/6 are useful prognostic predictors for chemotherapeutic effect in OC patients, and IGFBP2/4 are potential tumor markers for the diagnosis of OC.


1991 ◽  
Vol 129 (3) ◽  
pp. 459-464 ◽  
Author(s):  
H. S. Wang ◽  
J. Lim ◽  
J. English ◽  
L. Irvine ◽  
T. Chard

ABSTRACT Serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-1 (IGFBP-1) have been determined by radioimmunoassay in the maternal circulation (n = 91) and in the umbilical artery (n = 56) and vein (n = 90) of man. In both the umbilical artery and vein, the concentration of serum IGF-I showed an inverse correlation with birthweight (P < 0·005 and P < 0·001 respectively); the mean serum IGF-I levels in the small-for-gestational-age (SGA) group were significantly higher than those in average-for-gestational-age (AGA) neonates (P <0·01 and P < 0·001 respectively). However, maternal serum IGF-I showed no association with birthweight and there was no significant difference between the SGA and AGA groups. These observations imply that the production of IGF-I in the maternal and fetal compartments is independent and that there is unlikely to be transfer of IGF-I across the placenta. Serum IGFBP-1 levels in both maternal and umbilical cord blood (artery and vein) showed an inverse relation to birthweight (P <0·001, P<0·005 and P<0·001 respectively). Increased IGFBP-1 levels in the umbilical artery and vein were observed in the SGA group. These findings suggest that IGFBP-1 might inhibit the action of IGF-I in both the maternal and the fetal compartments and that the rise in IGFBP-1 could be a primary factor in retardation of fetal growth. Alternatively, circulating IGF-I and IGFBP-1 levels may only be a secondary reflection of local tissue events involved in fetal growth. Journal of Endocrinology (1991) 129, 459–464


1999 ◽  
Vol 36 (3) ◽  
pp. 155-166 ◽  
Author(s):  
Akira TSUKADA ◽  
Takeshi OHKUBO ◽  
Minoru TANAKA ◽  
Kunio NAKASHIMA ◽  
Masaaki WAKITA ◽  
...  

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