Molecular biology - HNFs - Linking the liver and pancreatic islets in diabetes

Harvard University, Cambridge, Massachusetts, United States
Science (Impact Factor: 33.61). 03/2004; 303(5662):1311-2. DOI: 10.1126/science.1095486
Source: PubMed
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    • "Moreover , they are also known to play an important role in the Theriogenology 68 (2007) 988–1002 occurrence of maturity-onset diabetes of the young (MODY) in humans [1] [2] [3] [4]. The variant homeo-domain containing families HNF-1 (a and b) and HNF-3 (a, b, and g, the winged helix/forkhead family in mammals) [4] [5] [6] not only regulate specific gene expression in the adult liver and other organs, but also are involved in: (1) various aspects of cellular metabolism [7] [8] [9] [10] [11] [12]; (2) expression of early-onset diabetes genes [7]; and (3) gastrulation events, e.g. "
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    ABSTRACT: Hepatocyte nuclear factors (HNF-1alpha, -1beta and -3beta) and insulin-like growth factors (IGF-I and -II), which are involved in liver-specific gene expression, metabolism, development and cell growth, have been found in the gonads of tilapia (Oreochromis mossambicus). However, the functions of these factors and how they interact within the gonads of bony fish are not understood. In the present study, we provided experimental evidence that the expression of HNF-3beta in the gonads of tilapia, but not HNF-1alpha and -1beta, was affected in vitro by 17beta-estradiol and hydrocortisone. Immunohistochemical staining confirmed that tilapia HNF-3beta was mainly found in the nuclei of hepatocytes, the follicular granulosa cells of the ovaries, and the interstitial cells of the testes of adult tilapia. Further data were gathered at various steroid concentrations (0.1, 1, 10, 100, and 1000 nM) over various culture intervals (6, 12, 18, 24, 30, and 36 h) and subjected to semi-quantitative RT-PCR analysis. The expression of downstream genes (IGF-I and -II) followed the same temporal patterns as HNF-3beta, albeit at decreased levels for 30 and 36 h culture intervals. Both hormones upregulated HNF-3beta mRNA expression at concentrations of 0.1-10 nM, and reached optimal physiological concentrations for induction of IGFs at 1-10 nM. The identity of the PCR fragments was concurrently verified by sequencing and PCR-Southern hybridization. We inferred that HNF-3beta and IGFs may play a regulatory role in tilapia gonads during oocyte maturation and spermatogenesis.
    Theriogenology 11/2007; 68(7):988-1002. DOI:10.1016/j.theriogenology.2007.07.016 · 1.80 Impact Factor
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    ABSTRACT: Abstract Several types of malignant epithelial liver tumors are recognized in infants, children and young adolescents. These neoplasms mainly include hepatoblastoma and its types and subtypes, whereas hepatocellular carcinoma is very rare in this age group. A pathology classification of hepatoblastomas has been worked out over the years, although some of the subtypes listed are still not sufficiently defined. Moreover, reviews of cases within large clinical trials have shown that an increasing number of pediatric hepatic tumors deviate from the phenotypes found in current classifications. The present overview refers to some of these apparently novel and intriguing lesions.
    Journal of Gastroenterology and Hepatology 12/2004; 19(s7). DOI:10.1111/j.1440-1746.2004.03706.x · 3.50 Impact Factor
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    ABSTRACT: Complex gene networks are responsible for the proper operation of the endocrine pancreas. A central member of such networks, the homeodomain transcription factor Pdx1, belongs to the ParaHox gene cluster, an array of Hox-like homeobox genes. With a combination of mRNA in situ hybridisation and immunodetection, we have found that the rest of ParaHox cluster genes, Cdx1, Cdx2/3, and Cdx4, and Gsh1 and Gsh2, are all expressed in specific islet cell types of the endocrine pancreas. To our knowledge, this is the first report that locates ParaHox genes other than Pdx1 and Cdx2/3 in a place as to be involved in the pancreatic transcriptional regulatory networks, potentially regulating glucagon-insulin homeostasis.
    Molecular and Cellular Endocrinology 07/2005; 237(1-2):59-66. DOI:10.1016/j.mce.2005.03.008 · 4.41 Impact Factor
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