Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1

TY - JOUR

T1 - Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1

AU - Serup, P

AU - Jensen, J

AU - Andersen, F G

AU - Jørgensen, Mette Christine

AU - Blume, N

AU - Holst, Jens Juul

AU - Madsen, O D

PY - 1996/8/20

Y1 - 1996/8/20

N2 - Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London) 371, 606-609]. In adults, IPF1 expression is restricted to the beta-cells in the islets of Langerhans. We report here that IPF1 induces expression of a subset of beta-cell-specific genes (insulin and islet amyloid polypeptide) when ectopically expressed in clones of transformed pancreatic islet alpha-cells. In contrast, expression of IPF1 in rat embryo fibroblasts factor failed to induce insulin and islet amyloid polypeptide expression. This is most likely due to the lack of at least one other essential insulin gene transcription factor, the basic helix-loop-helix protein Beta 2/NeuroD, which is expressed in both alpha- and beta-cells. We conclude that IPF1 is a potent transcriptional activator of endogenous insulin genes in non-beta islet cells, which suggests an important role of IPF1 in beta-cell maturation.

AB - Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London) 371, 606-609]. In adults, IPF1 expression is restricted to the beta-cells in the islets of Langerhans. We report here that IPF1 induces expression of a subset of beta-cell-specific genes (insulin and islet amyloid polypeptide) when ectopically expressed in clones of transformed pancreatic islet alpha-cells. In contrast, expression of IPF1 in rat embryo fibroblasts factor failed to induce insulin and islet amyloid polypeptide expression. This is most likely due to the lack of at least one other essential insulin gene transcription factor, the basic helix-loop-helix protein Beta 2/NeuroD, which is expressed in both alpha- and beta-cells. We conclude that IPF1 is a potent transcriptional activator of endogenous insulin genes in non-beta islet cells, which suggests an important role of IPF1 in beta-cell maturation.

KW - Amyloid

KW - Animals

KW - Anorexia

KW - Blood Glucose

KW - DNA-Binding Proteins

KW - Gene Expression Regulation

KW - Glucagon

KW - Glucagonoma

KW - Homeodomain Proteins

KW - Hypoglycemia

KW - Insulin

KW - Islet Amyloid Polypeptide

KW - Islets of Langerhans

KW - LIM-Homeodomain Proteins

KW - Neoplasms, Experimental

KW - Nerve Tissue Proteins

KW - Phenotype

KW - Rats

KW - Trans-Activators

KW - Transcription Factors

KW - Transcription, Genetic

KW - Transfection

KW - Tumor Cells, Cultured

M3 - Journal article

SN - 0027-8424

VL - 93

SP - 9015

EP - 9020

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 17

ER -