Growth hormone increases beta-cell proliferation in transplanted human and fetal rat islets.

OBJECTIVE The aim of the study was to increase the number of human islet beta-cells after transplantation with injections of human growth hormone (hGH). INTERVENTIONS Human islets and fetal rat islets were transplanted under the left kidney capsule and under the right kidney capsule, respectively in nude normoglycemic mice which were then given a daily injection of 200 microg hGH for 1-4 weeks. MAIN OUTCOME MEASURE Beta-cell proliferation was determined using thymidine incorporation and the beta-cell area was assessed using light microscopy. RESULTS Mice given hGH increased their body weight one week after transplantation and had a more efficient removal of glucose after 3 and 4 weeks. Treatment with hGH resulted in increased beta-cell proliferation in human and fetal rat beta-cells, and the beta-cell area tended to increase. However, serum insulin concentrations and pancreas insulin content remained unchanged. CONCLUSIONS hGH increased the proliferation of transplanted human beta-cells as well as improving the glucose tolerance of the transplanted mice.

[1]  A. Shapiro,et al.  Five-year follow-up after clinical islet transplantation. , 2005, Diabetes.

[2]  K. Ekdahl,et al.  Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation , 2002, The Lancet.

[3]  P. Gluckman,et al.  The effects of short-term administration of two low doses versus the standard GH replacement dose on insulin sensitivity and fasting glucose levels in young healthy adults. , 2002, The Journal of clinical endocrinology and metabolism.

[4]  B. Friedrichsen,et al.  Regulation of beta-cell mass by hormones and growth factors. , 2001, Diabetes.

[5]  G. Sonenshein,et al.  Growth hormone prevents apoptosis through activation of nuclear factor-kappaB in interleukin-3-dependent Ba/F3 cell line. , 2000, Molecular endocrinology.

[6]  E. Sullivan,et al.  The impact of recombinant human growth hormone treatment during chronic renal insufficiency on renal transplant recipients. , 2000, The Journal of pediatrics.

[7]  C. Vagianos,et al.  Growth hormone and insulin-like growth factor I protect intestinal cells from radiation induced apoptosis , 2000, Molecular and Cellular Endocrinology.

[8]  G. Elgue,et al.  Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? , 1999, Diabetes.

[9]  E. Bérard,et al.  Effects of growth hormone in short children after renal transplantation , 1998, Pediatric Nephrology.

[10]  E. Sullivan,et al.  Growth-hormone treatment of renal transplant recipients: the National Cooperative Growth Study experience--a report of the National Cooperative Growth Study and the North American Pediatric Renal Transplant Cooperative Study. , 1997, The Journal of pediatrics.

[11]  C. Svensson.  Effects of growth hormone in vitro on the glucose metabolism of fetal rat islet beta-cells. , 1996, Journal of Molecular Endocrinology.

[12]  R. Dalton,et al.  Effects of recombinant human growth hormone on renal function in children with renal transplants. , 1996, The Journal of pediatrics.

[13]  W. Hendrickson,et al.  Localization of Functional Receptor Epitopes on the Structure of Ciliary Neurotrophic Factor Indicates a Conserved, Function-related Epitope Topography among Helical Cytokines (*) , 1995, The Journal of Biological Chemistry.

[14]  P. Czernichow,et al.  Expression and regulation of growth hormone (GH) and prolactin (PRL) receptors in a rat insulin producing cell line (INS-1) , 1995, Molecular and Cellular Endocrinology.

[15]  B. Bengtsson,et al.  Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency. , 1993, Metabolism: clinical and experimental.

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

[17]  B. Tönshoff,et al.  Efficacy and safety of growth hormone treatment in short children with renal allografts: Three year experience , 1993 .

[18]  A. Atkinson,et al.  Influence of growth hormone on glucose-glucose 6-phosphate cycle and insulin action in normal humans. , 1992, The American journal of physiology.

[19]  R. Fine,et al.  Extended recombinant human growth hormone treatment after renal transplantation in children. , 1992, Journal of the American Society of Nephrology : JASN.

[20]  A. Rogol,et al.  Growth hormone-binding protein activity is inversely related to 24-hour growth hormone release in normal boys. , 1991, The Journal of clinical endocrinology and metabolism.

[21]  F. Reinholt,et al.  Acute renal graft rejection after treatment with human growth hormone , 1990, The Lancet.

[22]  O. Korsgren,et al.  Tissue culture of human fetal pancreas: growth hormone stimulates the formation and insulin production of islet-like cell clusters. , 1987, The Journal of clinical endocrinology and metabolism.

[23]  D. Hill,et al.  Growth Hormone Regulation of Somatomedin C/Insulin-Like Growth Factor I Production and DNA Replication in Fetal Rat Islets in Tissue Culture , 1987, Diabetes.

[24]  N. Billestrup,et al.  Growth hormone binding to specific receptors stimulates growth and function of cloned insulin-producing rat insulinoma RIN-5AH cells. , 1985, Endocrinology.

[25]  U. Adamson.  On the diabetogenic effect of growth hormone in man: effects of growth hormone on glucagon and insulin secretion , 1981, European journal of clinical investigation.

[26]  U. Adamson,et al.  Insulin-like and diabetogenic effects of growth hormone in healthy subjects, diabetics, and low insulin responders. , 1979, The Journal of clinical endocrinology and metabolism.

[27]  N. Freinkel,et al.  Method for Large-Scale Isolation of Pancreatic Islets by Tissue Culture of Fetal Rat Pancreas , 1979, Diabetes.

[28]  E. Cerasi,et al.  Acute suppressive effect of human growth hormone on basal insulin secretion in man. , 1975, Acta endocrinologica.

[29]  S. Fineberg,et al.  Acute Metabolic Effects of Human Growth Hormone , 1974, Diabetes.

[30]  Fineberg Se,et al.  Acute Metabolic Effects of Human Growth Hormone , 1974 .

[31]  L. Heding.  Determination of total serum insulin (IRI) in insulin-treated diabetic patients , 1972, Diabetologia.

[32]  P. Kelly,et al.  Growth hormone exerts antiapoptotic and proliferative effects through two different pathways involving nuclear factor-kappaB and phosphatidylinositol 3-kinase. , 2001, Endocrinology.

[33]  E. Bérard,et al.  Effects of growth hormone in short children after renal transplantation. French Society of Pediatric Nephrology. , 1998, Pediatric nephrology.

[34]  B. Tönshoff,et al.  Efficacy and safety of growth hormone treatment in short children with renal allografts: three year experience. Members of the German Study Group for Growth Hormone Treatment in Children with Renal Allografts. , 1993, Kidney international.