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A novel gene activated in regenerating islets
K Terazono1, H Yamamoto, S Takasawa
1Department of Biochemistry, Tohoku University School of Medicine, Miyagi, Japan.
Abstract:
Administration of poly(ADP-ribose) synthetase inhibitors such as nicotinamide to 90% depancreatized rats induces regeneration of pancreatic islets, thereby ameliorating the surgical diabetes (Yonemura, Y., Takashima, T., Miwa, K., Miyazaki, I., Yamamoto, H., and Okamoto, H. (1984) Diabetes 33, 401-404). In screening the regenerating islet-derived cDNA library, we came across a novel gene encoding a 165-amino acid protein. The gene was expressed in regenerating islets but not in normal pancreatic islets, insulinomas, or regenerating liver. In 90% depancreatized and nicotinamide-injected rats, the expression of the gene was increased 1 month after the partial pancreatectomy and reached a peak 3 months after the operation. The increase in expression of the gene was temporally correlated with the increase in size of regenerating islets and the decrease in urinary glucose level. The gene was also found to be activated in hyperplastic islets of aurothioglucose-treated mice. Thus, the expression of the gene in both regenerating and hyperplastic islets suggests possible roles for this gene in replication, growth, and maturation of islet beta-cells. We also found that a human pancreas-derived cDNA library contained a homologue to the gene.
Insights
Scientists discovered a new gene activated during pancreatic islet regeneration in rats. This gene
Area of Science:
- Molecular Biology
- Endocrinology
- Regenerative Medicine
Background:
- Poly(ADP-ribose) synthetase inhibitors, like nicotinamide, promote pancreatic islet regeneration in depancreatized rats, ameliorating surgical diabetes.
- Pancreatic islet regeneration is a complex process involving cellular growth and differentiation.
Purpose of the Study:
- To identify novel genes involved in pancreatic islet regeneration.
- To investigate the role of a newly identified gene in beta-cell replication, growth, and maturation.
Main Methods:
- Screening of a regenerating islet-derived cDNA library.
- Gene expression analysis in rat models of pancreatic regeneration (depancreatized and nicotinamide-injected) and hyperplastic islets (aurothioglucose-treated mice).
- Temporal correlation analysis of gene expression with islet size and urinary glucose levels.
- Identification of a human homologue in a human pancreas-derived cDNA library.
Main Results:
- A novel gene encoding a 165-amino acid protein was identified.
- The gene was specifically expressed in regenerating islets, not in normal islets, insulinomas, or regenerating liver.
- Gene expression increased significantly in regenerating islets of treated rats, correlating with islet growth and reduced urinary glucose.
- The gene was also activated in hyperplastic islets of aurothioglucose-treated mice.
- A human homologue of the gene was found.
Conclusions:
- The novel gene plays a potential role in the replication, growth, and maturation of pancreatic islet beta-cells.
- The findings suggest this gene as a potential therapeutic target for diabetes and other islet-related disorders.
- The presence of a human homologue indicates conserved function and potential translational applications.