Islet Neogenesis Associated Protein (INGAP) modulates gene expression in cultured neonatal rat islets
| Autor: | Silvana Bordin, Kelly Cristina Brandão da Silva, Hector Herminio del Zotto, Helena C. Barbosa, María Inés Borelli, Juan José Gagliardino, Antonio C. Boschero, Luiz Fabrizio Stoppiglia |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
endocrine system
medicine.medical_specialty DNA Complementary Potassium Channels Physiology medicine.medical_treatment Clinical Biochemistry USF1 Amylin Pancreatitis-Associated Proteins Biochemistry Islets of Langerhans Cellular and Molecular Neuroscience Endocrinology Antigens Neoplasm Internal medicine Insulin Secretion Gene expression Biomarkers Tumor medicine Animals Insulin Lectins C-Type RNA Messenger Rats Wistar Protein kinase A Cells Cultured Pancreatic hormone Oligonucleotide Array Sequence Analysis geography geography.geographical_feature_category biology Reverse Transcriptase Polymerase Chain Reaction Islet Peptide Fragments Rats Hepatocyte nuclear factors Glucose Gene Expression Regulation biology.protein Cytokines |
| Zdroj: | Regulatory Peptides. 136:78-84 |
| ISSN: | 0167-0115 |
| DOI: | 10.1016/j.regpep.2006.04.015 |
| Popis: | The Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion. We currently studied the effects of a pentadecapeptide having the 104-118 amino acid sequence of INGAP (INGAP-PP) on insulin secretion and on transcript profile expression in 4-day-cultured normal pancreatic neonatal rat islets. Islets cultured with INGAP-PP released significantly more insulin in response to 2.8 and 16.7 mM glucose than those cultured without the peptide. The macroarray analysis showed that 210 out of 2352 genes spotted in the nylon membranes were up-regulated while only 4 were down-regulated by INGAP-PP-treatment. The main categories of genes modified by INGAP-PP included several related with islet metabolism, insulin secretion mechanism, beta-cell mass and islet neogenesis. RT-PCR confirmed the macroarray results for ten selected genes involved in growing, maturation, maintenance of pancreatic islet-cells, and exocytosis, i.e., Hepatocyte nuclear factor 3beta (HNF3beta), Upstream stimulatory factor 1 (USF1), K(+)-channel proteins (SUR1 and Kir6.2), PHAS-I protein, Insulin 1 gene, Glucagon gene, Mitogen-activated protein kinase 1 (MAP3K1), Amylin (IAPP), and SNAP-25. INGAP-PP also stimulated PDX-1 expression. The expression of three transcripts (HNF3beta, SUR1, and SNAP-25) was confirmed by Western blotting for the corresponding proteins. In conclusion, our results show that INGAP-PP enhances specifically the secretion of insulin and the transcription of several islet genes, many of them directly or indirectly involved in the control of islet metabolism, beta-cell mass and islet neogenesis. These results, together with other previously reported, strongly indicate an important role of INGAP-PP, and possibly of INGAP, in the regulation of islet function and development. |
| Databáze: | OpenAIRE |
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