Tehmina Siddique1, Fazli Rabbi Awan2. 1. Diabetes and Cardio-Metabolic Disorders Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan. 2. Diabetes and Cardio-Metabolic Disorders Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan. Electronic address: awan.fr@gmail.com.
Abstract
OBJECTIVE: The endocrine regeneration of the pancreas holds great potential for stable diabetes therapy. The Regeneration (Reg) family of proteins has been associated with pancreas regeneration. Hence, the Reg3 delta bioactive peptide from a mouse was evaluated to see whether it can reverse hyperglycemia in a mouse model of diabetes with any effects on pancreatic gene expression. METHODS: In this study, we administrated the synthetic Reg3 delta bioactive peptide to healthy mice and to alloxan-induced mouse models of diabetes for 30 days, with weekly measurements of body weight and blood glucose levels. After 1 month, pancreatic gene profiling of these mice was performed for the Ngn-3, Pdx-1, MapK8, IGF-1, IGF2bp2, Reg3 beta and Reg3 delta genes. RESULTS: The glycemic levels in mice with diabetes were decreased significantly, restored almost to normal. Furthermore, the gene expression levels measured by quantitative polymerase chain reaction (qPCR) showed that messenger RNA (mRNA) levels of 2 important transcription factors (Ngn-3 and Pdx-1) were increased during the Reg3 delta peptide treatment. CONCLUSIONS: This study shows that Reg3 delta has the potential to reverse hyperglycemia by modulating gene expression in pancreatic endocrine precursor markers Pdx-1 and Ngn-3, which require further investigation at the protein and immunohistology levels.
OBJECTIVE: The endocrine regeneration of the pancreas holds great potential for stable diabetes therapy. The Regeneration (Reg) family of proteins has been associated with pancreas regeneration. Hence, the Reg3 delta bioactive peptide from a mouse was evaluated to see whether it can reverse hyperglycemia in a mouse model of diabetes with any effects on pancreatic gene expression. METHODS: In this study, we administrated the synthetic Reg3 delta bioactive peptide to healthy mice and to alloxan-induced mouse models of diabetes for 30 days, with weekly measurements of body weight and blood glucose levels. After 1 month, pancreatic gene profiling of these mice was performed for the Ngn-3, Pdx-1, MapK8, IGF-1, IGF2bp2, Reg3 beta and Reg3 delta genes. RESULTS: The glycemic levels in mice with diabetes were decreased significantly, restored almost to normal. Furthermore, the gene expression levels measured by quantitative polymerase chain reaction (qPCR) showed that messenger RNA (mRNA) levels of 2 important transcription factors (Ngn-3 and Pdx-1) were increased during the Reg3 delta peptide treatment. CONCLUSIONS: This study shows that Reg3 delta has the potential to reverse hyperglycemia by modulating gene expression in pancreatic endocrine precursor markers Pdx-1 and Ngn-3, which require further investigation at the protein and immunohistology levels.