Regulation of beta-cell mass by hormones and growth factors.

Substantial new information has accumulated on molecular mechanisms of pancreas development, regulation of beta-cell gene expression, and the role of growth factors in the differentiation, growth, and regeneration of beta-cells. The present review focuses on some recent studies on the mechanism of action of cytokines such as growth hormone (GH) and prolactin (PRL) in beta-cell proliferation and gene expression-in particular, the role of signal transducers and activators of transcription (STAT) proteins. The implication of the discovery of suppressors of cytokine signaling (SOCS) proteins for the interaction between stimulatory and inhibitory cytokines, including GH, PRL, leptin, and the proinflammatory cytokines interleukin-1 and interferon-gamma, in beta-cell survival is not yet clear. Recent studies indicate a role of cell adhesion molecules and the delta-like protein preadipocyte factor 1/fetal antigen 1 (Pref-1/FA-1) in cytokine-induced beta-cell growth and development. Surprisingly, glucagon-like peptide-1 (GLP-1) was recently found to stimulate not only insulin secretion but also beta-cell replication and differentiation, which may present a new perspective in treatment of type 2 diabetes. Together with the intriguing reports on positive effects of insulin on both beta-cell growth and function, a picture is emerging of an integrated network of signaling events acting in concert to control beta-cell mass adaptation to insulin demand.

[1]  P. Meda,et al.  Importance of cell-matrix interactions in rat islet beta-cell secretion in vitro: role of alpha6beta1 integrin. , 2000, Diabetes.

[2]  J. Ihle,et al.  Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. , 1999, Immunity.

[3]  G. Korbutt,et al.  Transfection of human pancreatic islets with an anti-apoptotic gene (bcl-2) protects beta-cells from cytokine-induced destruction. , 1999, Diabetes.

[4]  J. Nielsen,et al.  Growth hormone action in rat insulinoma cells expressing truncated growth hormone receptors. , 1991, The Journal of biological chemistry.

[5]  P. Serup,et al.  Molecular basis for islet development, growth, and regeneration , 1998 .

[6]  J. Schwartz,et al.  Molecular mechanism of growth hormone action. , 1996, Annual review of physiology.

[7]  J. Nielsen,et al.  Cytoplasmic sequences of the growth hormone receptor necessary for signal transduction. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Itaru Matsumura,et al.  Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine‐dependent growth of hematopoietic cells , 1999, The EMBO journal.

[9]  S. Gisselbrecht.  The CIS/SOCS proteins: a family of cytokine-inducible regulators of signaling. , 1999, European cytokine network.

[10]  J. Nielsen,et al.  Regulation of Prolactin Receptor (PRLR) Gene Expression in Insulin-producing Cells , 1999, The Journal of Biological Chemistry.

[11]  J. Nielsen,et al.  Growth Hormone and Prolactin Stimulate the Expression of Rat Preadipocyte Factor-1/Δ-Like Protein in Pancreatic Islets: Molecular Cloning and Expression Pattern during Development and Growth of the Endocrine Pancreas. , 1997, Endocrinology.

[12]  P. Czernichow,et al.  Growth hormone (GH) and prolactin (PRL) regulate IGFBP-3 gene expression in rat β-cells , 1995, Molecular and Cellular Endocrinology.

[13]  J. Nielsen,et al.  Effects of sex and pregnancy hormones on growth hormone and prolactin receptor gene expression in insulin-producing cells. , 1993, Endocrinology.

[14]  M. Prentki,et al.  Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)-cells , 1999, Diabetologia.

[15]  Prolactin regulation of islet-derived INS-1 cells: characteristics and immunocytochemical analysis of STAT5 translocation. , 1997, Endocrinology.

[16]  M. White,et al.  Insulin-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is glucose-dependent. Synergistic activation of insulin receptor substrate-mediated signal transduction pathways by glucose and IGF-I in INS-1 cells. , 1998, The Journal of biological chemistry.

[17]  L. Villa-komaroff,et al.  Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Y. Hosokawa,et al.  Induction of D2 and D3 cyclin-encoding genes during promotion of the G1/S transition by prolactin in rat Nb2 cells. , 1994, Gene.

[19]  J. Nielsen,et al.  Developmental expression of proprotein convertase 1/3 in the rat , 1999, Molecular and Cellular Endocrinology.

[20]  J. Nielsen,et al.  The stimulatory effect of growth hormone, prolactin, and placental lactogen on beta-cell proliferation is not mediated by insulin-like growth factor-I. , 1991, Endocrinology.

[21]  P. Serup,et al.  Identification of a growth hormone-responsive STAT5-binding element in the rat insulin 1 gene. , 1996, Molecular endocrinology.

[22]  John Calvin Reed,et al.  Prolactin-regulated apoptosis of Nb2 lymphoma cells , 1998, Endocrine.

[23]  H. Lodish,et al.  Fetal Anemia and Apoptosis of Red Cell Progenitors in Stat5a−/−5b−/− Mice A Direct Role for Stat5 in Bcl-XL Induction , 1999, Cell.

[24]  L. Yu-Lee,et al.  Transcriptional Inhibition by Stat5 , 1997, The Journal of Biological Chemistry.

[25]  Jie Zhou,et al.  Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon- and insulin-producing cells. , 1999, Diabetes.

[26]  V. Emilsson,et al.  Leptin signalling in pancreatic islets and clonal insulin-secreting cells. , 1999, Journal of molecular endocrinology.

[27]  J. Nielsen,et al.  Growth hormone receptor C-terminal domains required for growth hormone-induced intracellular free Ca2+ oscillations and gene transcription. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[28]  T. Fujikawa,et al.  Cooperative and differential effects of estrogen, prolactin, 22K and 20K human growth hormones on cyclin D1/PRAD1 gene expression in T‐47D human breast cancer cells , 1998, Biochemistry and molecular biology international.

[29]  D. Hilton,et al.  Growth Hormone Preferentially Induces the Rapid, Transient Expression of SOCS-3, a Novel Inhibitor of Cytokine Receptor Signaling* , 1998, The Journal of Biological Chemistry.

[30]  Nielsen Jh.  Growth and function of the pancreatic beta cell in vitro: effects of glucose, hormones and serum factors on mouse, rat and human pancreatic islets in organ culture. , 1985 .

[31]  C. Wollheim,et al.  Postreceptor signalling of growth hormone and prolactin and their effects in the differentiated insulin-secreting cell line, INS-1. , 1996, Endocrinology.