David Clemmons

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. pmc Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes
    David R Clemmons
    Division of Endocrinology, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 7170, USA
    Endocrinol Metab Clin North Am 41:425-43, vii-viii. 2012
  2. ncbi request reprint IGF-I assays: current assay methodologies and their limitations
    David R Clemmons
    CB 7170, 8024 Burnett Womack, Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7170, USA
    Pituitary 10:121-8. 2007
  3. ncbi request reprint The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity
    D R Clemmons
    Department of Medicine, University of North Carolina, Chapel Hill 27599 7170, USA
    J Clin Endocrinol Metab 85:1518-24. 2000
  4. ncbi request reprint Clinical utility of measurements of insulin-like growth factor 1
    David R Clemmons
    University of North Carolina School of Medicine, Chapel Hill, NC, USA
    Nat Clin Pract Endocrinol Metab 2:436-46. 2006
  5. ncbi request reprint Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm
    David R Clemmons
    University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    J Clin Endocrinol Metab 88:4759-67. 2003
  6. ncbi request reprint Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes
    D R Clemmons
    Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    J Clin Endocrinol Metab 92:2652-8. 2007
  7. ncbi request reprint Interaction between insulin-like growth factor-I receptor and alphaVbeta3 integrin linked signaling pathways: cellular responses to changes in multiple signaling inputs
    D R Clemmons
    Department of Medicine, Division of Endocrinology, University of North Carolina School of Medicine, CB 7170, Chapel Hill, North Carolina 27599, USA
    Mol Endocrinol 19:1-11. 2005
  8. pmc Role of the integrin alphaVbeta3 in mediating increased smooth muscle cell responsiveness to IGF-I in response to hyperglycemic stress
    David R Clemmons
    Department of Medicine, Division of Endocrinology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599, USA
    Growth Horm IGF Res 17:265-70. 2007
  9. ncbi request reprint Value of insulin-like growth factor system markers in the assessment of growth hormone status
    David R Clemmons
    Division of Endocrinology, University of North Carolina School of Medicine, University of North Carolina, CB 7170, 8024 Burnett Womack, Chapel Hill, NC 27599, USA
    Endocrinol Metab Clin North Am 36:109-29. 2007
  10. ncbi request reprint Involvement of insulin-like growth factor-I in the control of glucose homeostasis
    David R Clemmons
    CB 7170, 8024 Burnett Womack, Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7170, USA
    Curr Opin Pharmacol 6:620-5. 2006

Collaborators

Detail Information

Publications72

  1. pmc Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes
    David R Clemmons
    Division of Endocrinology, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 7170, USA
    Endocrinol Metab Clin North Am 41:425-43, vii-viii. 2012
    ..However, patients with diabetes are also sensitive to stimulation of side effects in response to IGF-I. IGF-I coordinately links growth hormone and insulin actions and has direct effects on intermediary metabolism...
  2. ncbi request reprint IGF-I assays: current assay methodologies and their limitations
    David R Clemmons
    CB 7170, 8024 Burnett Womack, Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7170, USA
    Pituitary 10:121-8. 2007
    ..A future goal should be the development of standard procedures and reagents that eliminate this degree of variability...
  3. ncbi request reprint The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity
    D R Clemmons
    Department of Medicine, University of North Carolina, Chapel Hill 27599 7170, USA
    J Clin Endocrinol Metab 85:1518-24. 2000
    ..Further studies will be required to determine the long-term safety and efficacy of this combination in patients with insulin resistance and diabetes...
  4. ncbi request reprint Clinical utility of measurements of insulin-like growth factor 1
    David R Clemmons
    University of North Carolina School of Medicine, Chapel Hill, NC, USA
    Nat Clin Pract Endocrinol Metab 2:436-46. 2006
    ..IGF-I is also very useful in monitoring the symptomatic response to therapy...
  5. ncbi request reprint Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm
    David R Clemmons
    University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    J Clin Endocrinol Metab 88:4759-67. 2003
    ..Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs...
  6. ncbi request reprint Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes
    D R Clemmons
    Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    J Clin Endocrinol Metab 92:2652-8. 2007
    ..The changes in various components of the IGF system that occur in response to rhIGF-I/rhIGFBP-3 as well as the minimum effective dose have not been determined...
  7. ncbi request reprint Interaction between insulin-like growth factor-I receptor and alphaVbeta3 integrin linked signaling pathways: cellular responses to changes in multiple signaling inputs
    D R Clemmons
    Department of Medicine, Division of Endocrinology, University of North Carolina School of Medicine, CB 7170, Chapel Hill, North Carolina 27599, USA
    Mol Endocrinol 19:1-11. 2005
    ..Thus, within the vessel wall, a mechanism exists whereby ligand occupancy of the alphaVbeta3 integrin is required for assembly of a multicomponent membrane signaling complex that is necessary for cells to respond optimally to IGF-I...
  8. pmc Role of the integrin alphaVbeta3 in mediating increased smooth muscle cell responsiveness to IGF-I in response to hyperglycemic stress
    David R Clemmons
    Department of Medicine, Division of Endocrinology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599, USA
    Growth Horm IGF Res 17:265-70. 2007
    ..These findings indicate that in SMC hyperglycemic stress leads to altered IGF-I signaling, which allows the cells to undergo a mitogenic response, and which may contribute to the development of atherosclerosis...
  9. ncbi request reprint Value of insulin-like growth factor system markers in the assessment of growth hormone status
    David R Clemmons
    Division of Endocrinology, University of North Carolina School of Medicine, University of North Carolina, CB 7170, 8024 Burnett Womack, Chapel Hill, NC 27599, USA
    Endocrinol Metab Clin North Am 36:109-29. 2007
    ..Free IGF-I, IGF binding protein-3, or acid-labile subunit may provide useful information regarding GH secretion in specific conditions but are not superior to IGF-I for making the diagnosis of GH deficiency or acromegaly...
  10. ncbi request reprint Involvement of insulin-like growth factor-I in the control of glucose homeostasis
    David R Clemmons
    CB 7170, 8024 Burnett Womack, Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7170, USA
    Curr Opin Pharmacol 6:620-5. 2006
    ..It also decreases insulin requirement in patients with insulin-deficient diabetes. Taken together, these findings suggest that IGF-I is functioning coordinately with insulin to regulate glucose homeostasis...
  11. ncbi request reprint Role of insulin-like growth factor iin maintaining normal glucose homeostasis
    David R Clemmons
    Department of Medicine, UNC School of Medicine, Chapel Hill, NC 27599, USA
    Horm Res 62:77-82. 2004
    ..Taken together, these findings support the conclusion that IGF-I is necessary for normal insulin sensitivity, and impairment of IGF-I synthesis results in a worsening state of insulin resistance...
  12. ncbi request reprint Quantitative measurement of IGF-I and its use in diagnosing and monitoring treatment of disorders of growth hormone secretion
    David R Clemmons
    Division of Endocrinology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7170, USA
    Endocr Dev 9:55-65. 2005
    ..Careful attention to these characteristics is likely to result in valid and useful IGF-I assay results...
  13. ncbi request reprint Tyrosine phosphorylation of the beta3-subunit of the alphaVbeta3 integrin is required for embrane association of the tyrosine phosphatase SHP-2 and its further recruitment to the insulin-like growth factor I receptor
    Yan Ling
    CB 7170, 6111 Thurston Bowles, Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170
    Mol Endocrinol 17:1824-33. 2003
    ..This was associated with prolonged IGF-IR phosphorylation and an impaired cellular DNA synthesis response to IGF-I. These results define a mechanism by which ligand occupancy of alphaVbeta3 regulates the SMC response to IGF-I...
  14. ncbi request reprint Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer
    David R Clemmons
    Division of Endocrinology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Nat Rev Drug Discov 6:821-33. 2007
    ..Therefore, inhibiting IGF1 action has been proposed as a specific mechanism for potentiating the effects of existing anticancer therapies or for directly inhibiting tumour cell growth...
  15. doi request reprint Long-acting forms of growth hormone-releasing hormone and growth hormone: effects in normal volunteers and adults with growth hormone deficiency
    David R Clemmons
    School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Horm Res 68:178-81. 2007
    ....
  16. ncbi request reprint Igf-I signaling in response to hyperglycemia and the development of diabetic complications
    David Clemmons
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, NC 27599 7170, USA
    Curr Diabetes Rev 7:235-45. 2011
    ..This may be an important variable for determining the progression of atherosclerosis in poorly controlled diabetes and in the development of retinopathy...
  17. ncbi request reprint Use of mutagenesis to probe IGF-binding protein structure/function relationships
    D R Clemmons
    Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Endocr Rev 22:800-17. 2001
    ..These results have revealed that discrete regions of IGFBP sequence can mediate important and specific functional properties of these proteins...
  18. ncbi request reprint Vitronectin binding to IGF binding protein-5 (IGFBP-5) alters IGFBP-5 modulation of IGF-I actions
    Taek Nam
    Division of Endocrinology, University of North Carolina, Chapel Hill, NC 27599, USA
    Endocrinology 143:30-6. 2002
    ....
  19. doi request reprint Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays
    David R Clemmons
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7170, USA
    Clin Chem 57:555-9. 2011
    ..This group recommends that a commutable standard for each assay be implemented for worldwide use and that its recommendations be applied to accomplish the task of providing reliable and clinically useful results...
  20. doi request reprint Clinical laboratory indices in the treatment of acromegaly
    David R Clemmons
    Department of Medicine, UNC, Chapel Hill, NC 27599, United States
    Clin Chim Acta 412:403-9. 2011
    ..For the long term assessment of outcome and clinical disease activity measurement of both hormones is recommended...
  21. doi request reprint The diagnosis and treatment of growth hormone deficiency in adults
    David R Clemmons
    Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    Curr Opin Endocrinol Diabetes Obes 17:377-83. 2010
    ..Additionally, a consensus conference has been held regarding needed improvements in diagnostic testing and the recommendations of consensus panels regarding diagnostic criteria and laboratory test utilization are summarized...
  22. ncbi request reprint Recombinant, nonglycosylated human insulin-like growth factor-binding protein-3 (IGFBP-3) is degraded preferentially after administration to type II diabetics, resulting in increased endogenous glycosylated IGFBP-3
    D R Clemmons
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Clin Endocrinol Metab 90:6561-8. 2005
    ..One determinant of IGFBP-3 stability is proteolysis. Normal subjects have minimal IGFBP-3 protease activity; however, with pregnancy, acute catabolic illness, or diabetes, IGFBP-3 protease activity is increased...
  23. ncbi request reprint Inhibition of insulin-like growth factor binding protein 5 proteolysis in articular cartilage and joint fluid results in enhanced concentrations of insulin-like growth factor 1 and is associated with improved osteoarthritis
    David R Clemmons
    Division of Endocrinology, University of North Carolina, Chapel Hill, 27599 7170, USA
    Arthritis Rheum 46:694-703. 2002
    ....
  24. ncbi request reprint Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose
    D R Clemmons
    Division of Endocrinology, Department of Medicine, University of North Carolina, 6111A Thurston Bowles, CB 7170, Chapel Hill, NC 27599, USA
    Growth Horm IGF Res 15:265-74. 2005
    ..Coadministration of IGFBP-3 with IGF-I produces lower free IGF-I (Tmax and Cmax) levels compared to administration of IGF-I alone and is associated with relatively low incidence of side effects during 2 weeks of administration...
  25. ncbi request reprint DOK1 mediates SHP-2 binding to the alphaVbeta3 integrin and thereby regulates insulin-like growth factor I signaling in cultured vascular smooth muscle cells
    Yan Ling
    University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 280:3151-8. 2005
    ..These results demonstrate that DOK1 mediates SHP-2/beta3 association in response to IGF-I thereby mediating the effect of integrin ligand occupancy on IGF-IR-linked signaling in smooth muscle cells...
  26. ncbi request reprint Integrin-associated protein binding domain of thrombospondin-1 enhances insulin-like growth factor-I receptor signaling in vascular smooth muscle cells
    Laura A Maile
    Division of Endocrinology, University of North Carolina, Chapel Hill, NC 27599 7170, USA
    Circ Res 93:925-31. 2003
    ..These observations support the conclusion that thrombospondin-1 and IGF-I seem to function coordinately in stimulating smooth muscle proliferation via the thrombospondin-1 interaction with IAP...
  27. pmc p66shc negatively regulates insulin-like growth factor I signal transduction via inhibition of p52shc binding to Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 leading to impaired growth factor receptor-bound protein-2 membrane
    Gang Xi
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
    Mol Endocrinol 22:2162-75. 2008
    ....
  28. ncbi request reprint Expression of the human beta3 integrin subunit in mouse smooth muscle cells enhances IGF-I-stimulated signaling and proliferation
    Gang Xi
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina, USA
    J Cell Physiol 214:306-15. 2008
    ..These results strongly support the conclusion that optimal SMC responsiveness to IGF-I requires ligand interaction with the C-loop domain of hbeta3...
  29. pmc Role of SHPS-1 in the regulation of insulin-like growth factor I-stimulated Shc and mitogen-activated protein kinase activation in vascular smooth muscle cells
    Yan Ling
    School of Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, USA
    Mol Biol Cell 16:3353-64. 2005
    ..We conclude that SHPS-1 functions as an anchor protein that recruits both Shc and SHP-2 and that their recruitment is necessary for IGF-I-dependent Shc phosphorylation, which is required for an optimal mitogenic response in SMCs...
  30. pmc The association between integrin-associated protein and SHPS-1 regulates insulin-like growth factor-I receptor signaling in vascular smooth muscle cells
    Laura A Maile
    Division of Endocrinology, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Mol Biol Cell 14:3519-28. 2003
    ....
  31. pmc Insulin-like growth factor-I-stimulated insulin receptor substrate-1 negatively regulates Src homology 2 domain-containing protein-tyrosine phosphatase substrate-1 function in vascular smooth muscle cells
    Yashwanth Radhakrishnan
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 285:15682-95. 2010
    ..We conclude that IRS-1 is an important factor for maintaining VSMCs in the non-proliferative state and that its down-regulation is a component of the VSMC response to hyperglycemic stress that results in an enhanced response to IGF-I...
  32. ncbi request reprint Regulation of igf-I signaling in retinal endothelial cells by hyperglycemia
    Emily C Miller
    Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    Invest Ophthalmol Vis Sci 48:3878-87. 2007
    ..To investigate the role of hyperglycemia in regulating the proliferative response of retinal endothelial cells (RECs) to insulin-like growth factor (IGF)-I...
  33. ncbi request reprint Recruitment of the tyrosine phosphatase Src homology 2 domain tyrosine phosphatase-2 to the p85 subunit of phosphatidylinositol-3 (PI-3) kinase is required for insulin-like growth factor-I-dependent PI-3 kinase activation in smooth muscle cells
    Mijin Kwon
    Division of Endocrinology, 6111 Thurston Bowles, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    Endocrinology 147:1458-65. 2006
    ..SHP-2 recruitment to p85 is required for IGF-I-stimulated association of the p85/p110 complex with insulin receptor substrate-1 and for the subsequent activation of the PI-3 kinase pathway leading to increased cell migration...
  34. ncbi request reprint The alphaVbeta3 integrin regulates insulin-like growth factor I (IGF-I) receptor phosphorylation by altering the rate of recruitment of the Src-homology 2-containing phosphotyrosine phosphatase-2 to the activated IGF-I receptor
    Laura A Maile
    University of North Carolina Department of Medicine, Division of Endocrinology and Metabolism, Chapel Hill, North Carolina 27599 7170, USA
    Endocrinology 143:4259-64. 2002
    ....
  35. pmc Hyperglycemia-induced p66shc inhibits insulin-like growth factor I-dependent cell survival via impairment of Src kinase-mediated phosphoinositide-3 kinase/AKT activation in vascular smooth muscle cells
    Gang Xi
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
    Endocrinology 151:3611-23. 2010
    ....
  36. pmc PDK1 recruitment to the SHPS-1 signaling complex enhances insulin-like growth factor-i-stimulated AKT activation and vascular smooth muscle cell survival
    Xinchun Shen
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 285:29416-24. 2010
    ..These findings reveal a novel mechanism for recruitment of PDK1 to the SHPS-1 signaling complex, which is required for IGF-I-stimulated AKT Thr(308) phosphorylation and inhibition of apoptosis...
  37. ncbi request reprint Insulin-like growth factor binding protein-5 (IGFBP-5) interacts with thrombospondin-1 to induce negative regulatory effects on IGF-I actions
    Anna M Moralez
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, NC 27599, USA
    J Cell Physiol 203:328-34. 2005
    ....
  38. pmc p66shc inhibits insulin-like growth factor-I signaling via direct binding to Src through its polyproline and Src homology 2 domains, resulting in impairment of Src kinase activation
    Gang Xi
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 285:6937-51. 2010
    ..These findings demonstrate that p66(shc) utilizes a novel mechanism for modulating Src kinase activation and that this interaction is mediated through both its collagen homologous region 2 and Src homology 2 domains...
  39. doi request reprint Glucose-oxidized low-density lipoproteins enhance insulin-like growth factor I-stimulated smooth muscle cell proliferation by inhibiting integrin-associated protein cleavage
    Lee B Allen
    Department of Medicine, Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    Endocrinology 150:1321-9. 2009
    ..In conclusion, these data provide a molecular mechanism to explain previous studies that have reported an enhancing effect of g-OxLDL on IGF-I-stimulated SMC proliferation...
  40. ncbi request reprint IGF-I/IGF-binding protein-3 combination improves insulin resistance by GH-dependent and independent mechanisms
    Thomas O'Connell
    Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Clin Endocrinol Metab 87:4356-60. 2002
    ..These findings necessitate further studies into the non-GH-related mechanism by which IGF-I enhances insulin sensitivity...
  41. ncbi request reprint Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant
    Ariel L Barkan
    Department of Internal Medicine, University of Michigan Medical Center, 3920 Taubman Center, Ann Arbor, Michigan 48109 0354, USA
    J Clin Endocrinol Metab 90:5684-91. 2005
    ..In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported...
  42. ncbi request reprint Regulation of vascular smooth muscle cell responses to insulin-like growth factor (IGF)-I by local IGF-binding proteins
    Tzefu Hsieh
    Department of Molecular, Cellular, and Developmental Biology, The University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 278:42886-92. 2003
    ..IGFBP-5 not only modulates IGF-I actions, but it also stimulates cell migration by interacting with cell-surface heparan sulfate proteoglycans...
  43. ncbi request reprint The role of Src kinase in insulin-like growth factor-dependent mitogenic signaling in vascular smooth muscle cells
    Jaroslava Lieskovska
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7170, USA
    J Biol Chem 281:25041-53. 2006
    ..Upon IGF-I stimulation, a complex assembles on SHPS-1 that contains SHP-2, c-Src, and Shc wherein Src phosphorylates Shc, a signaling step that is necessary for an optimal mitogenic response...
  44. ncbi request reprint Increases in free, unbound insulin-like growth factor I enhance insulin responsiveness in human hepatoma G2 cells in culture
    Keiji Sakai
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:13620-7. 2002
    ..IGFBP-1 complexes. This released IGF-I stimulates biologic actions that are mediated predominantly through the IGF-I/insulin hybrid receptor...
  45. pmc Insulin-like growth factor-I stimulates Shc-dependent phosphatidylinositol 3-kinase activation via Grb2-associated p85 in vascular smooth muscle cells
    Yashwanth Radhakrishnan
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 283:16320-31. 2008
    ..We conclude that in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration...
  46. ncbi request reprint Control of insulin-like growth factor binding protein-5 protease synthesis and secretion by human fibroblasts and porcine aortic smooth muscle cells
    Anna Moralez
    Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Endocrinology 144:2489-95. 2003
    ..This increase results in a net increase in IGFBP-5 proteolysis, which has the potential to modify IGF-I and IGFBP-5 actions...
  47. pmc Identification of novel SHPS-1-associated proteins and their roles in regulation of insulin-like growth factor-dependent responses in vascular smooth muscle cells
    Xinchun Shen
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
    Mol Cell Proteomics 8:1539-51. 2009
    ....
  48. doi request reprint A monoclonal antibody against alphaVbeta3 integrin inhibits development of atherosclerotic lesions in diabetic pigs
    Laura A Maile
    Division of Endocrinology, University of North Carolina, Chapel Hill, NC 27599 7170, USA
    Sci Transl Med 2:18ra11. 2010
    ..This approach offers a potential therapeutic approach to the treatment of this disorder...
  49. ncbi request reprint Regulation of insulin-like growth factor I receptor dephosphorylation by SHPS-1 and the tyrosine phosphatase SHP-2
    Laura A Maile
    Division of Endocrinology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:8955-60. 2002
    ..Recruitment of SHP-2 to the receptor then results in receptor dephosphorylation. The regulation of this process may be an important determinant of IGF-IR-mediated signaling...
  50. pmc Identification of compounds that inhibit IGF-I signaling in hyperglycemia
    Laura A Maile
    Division of Endocrinology, The University of North Carolina at Chapel Hill, NC 27599 7170, USA
    Exp Diabetes Res 2009:267107. 2009
    ..Identification of these compounds that utilize this mechanism has the potential to yield novel therapeutic approaches for the prevention and treatment of vascular complications associated with diabetes...
  51. doi request reprint Role of IGF-I in skeletal muscle mass maintenance
    David R Clemmons
    Division of Endocrinology, University of North Carolina School of Medicine, hapel Hill, NC 27599 7170, USA
    Trends Endocrinol Metab 20:349-56. 2009
    ..Because there are no approved medical therapies that will reverse catabolism at present, this represents an opportunity to fulfill a major unmet medical need...
  52. pmc Modulation of integrin antagonist signaling by ligand binding of the heparin-binding domain of vitronectin to the alphaVbeta3 integrin
    Laura A Maile
    Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    J Cell Biochem 105:437-46. 2008
    ....
  53. ncbi request reprint Growth hormone receptor antagonist improves insulin resistance in acromegaly
    D Roderick Rose
    Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Growth Horm IGF Res 12:418-24. 2002
    ..The results suggest a potential role for Pevisomant in the treatment of insulin resistant states other than acromegaly...
  54. pmc Glucose regulation of integrin-associated protein cleavage controls the response of vascular smooth muscle cells to insulin-like growth factor-I
    Laura A Maile
    Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7170, USA
    Mol Endocrinol 22:1226-37. 2008
    ....
  55. ncbi request reprint Minireview: Integral membrane proteins that function coordinately with the insulin-like growth factor I receptor to regulate intracellular signaling
    David R Clemmons
    Department of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Endocrinology 144:1664-70. 2003
    ..Determination of the spectrum of ligands for these three integral membrane proteins and the mechanisms by which each ligand functions to alter IGF-I signaling are important objectives of future research...
  56. pmc The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity
    David R Clemmons
    Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Clin Invest 113:25-7. 2004
    ..A new study (see the related article beginning on page 96) shows that blocking the effect of GH in the presence of low serum IGF-1 concentrations enhances insulin sensitivity...
  57. ncbi request reprint Hyperglycemia alters the responsiveness of smooth muscle cells to insulin-like growth factor-I
    Laura A Maile
    Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Endocrinology 148:2435-43. 2007
    ....
  58. ncbi request reprint Insulin-like growth factor-I signaling in smooth muscle cells is regulated by ligand binding to the 177CYDMKTTC184 sequence of the beta3-subunit of alphaVbeta3
    Laura A Maile
    Division of Endocrinology, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Mol Endocrinol 20:405-13. 2006
    ..In conclusion, we have demonstrated that the 177-184 sequence of beta3 is necessary for Vn binding to alphaVbeta3 and that ligand occupancy of this site is necessary for an optimal response of smooth muscle cells to IGF-I...
  59. ncbi request reprint Insulin-like growth factor I increases alpha Vbeta 3 affinity by increasing the amount of integrin-associated protein that is associated with non-raft domains of the cellular membrane
    Laura A Maile
    University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    J Biol Chem 277:1800-5. 2002
    ..IGF-I-stimulated translocation of IAP and increase in IAP-alpha(V)beta(3) association represent an important process by which IGF-I modulates alpha(V)beta(3) ligand binding and cellular responses...
  60. ncbi request reprint The heparin binding domain of vitronectin is the region that is required to enhance insulin-like growth factor-I signaling
    Laura A Maile
    Division of Endocrinology, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Mol Endocrinol 20:881-92. 2006
    ..We conclude that the interaction of the HBD of Vn binding to the cysteine loop sequence of beta3 is necessary and sufficient for the positive effects of Vn on IGF-I-mediated effects in smooth muscle cells...
  61. pmc Integrin-associated protein association with SRC homology 2 domain containing tyrosine phosphatase substrate 1 regulates igf-I signaling in vivo
    Laura A Maile
    Division of Endocrinology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    Diabetes 57:2637-43. 2008
    ..The aim of this study was to determine whether signaling events that have been shown to be required for stimulation of SMC growth were regulated by glucose concentrations in vivo...
  62. ncbi request reprint SOM230 inhibits insulin-like growth factor-I action in mammary gland development by pituitary independent mechanism: mediated through somatostatin subtype receptor 3?
    Weifeng Ruan
    Neuroendocrine Unit, New York University School of Medicine, New York, New York 10016, USA
    Mol Endocrinol 20:426-36. 2006
    ....
  63. pmc The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate
    J Christopher Fritton
    Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 285:4709-14. 2010
    ....
  64. doi request reprint Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells
    Xinchun Shen
    Department of Medicine, University of North Carolina, Chapel Hill, 27599, USA
    Cell Mol Life Sci 67:3893-903. 2010
    ..Thus, Pyk2 recruitment to SHPS-1 plays an important role in regulating the IGF-I-stimulated mitogenic response...
  65. pmc IGF-1 and bone: New discoveries from mouse models
    Shoshana Yakar
    Division of Endocrinology, University of North Carolina, Chapel Hill, NC, USA
    J Bone Miner Res 25:2543-52. 2010
    ..In this review we present new and old findings from mouse models of the IGF system and discuss their clinical relevance to normal and pathological skeletal physiology...
  66. ncbi request reprint Role of insulin-like growth factor-I in diagnosis and management of acromegaly
    David R Clemmons
    Department of Medicine, Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7170, USA
    Endocr Pract 10:362-71. 2004
    ..To highlight the use of insulin-like growth factor-I (IGF-I) measurements in the management of acromegaly...
  67. pmc AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation
    Junyu Ning
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27705, USA
    Mol Endocrinol 24:1218-29. 2010
    ..Because IGF-I is an important stimulant of the anabolic response, this effect of AMPK could account for part of its inhibitory effect on protein synthesis, thus allowing more efficient energy use by other cellular processes...
  68. ncbi request reprint Monitoring the response to treatment in acromegaly
    David R Clemmons
    J Clin Endocrinol Metab 89:5289-91. 2004
  69. ncbi request reprint Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency?
    Mark L Hartman
    Lilly Research Laboratories, Indianapolis, Indiana 46285, USA
    J Clin Endocrinol Metab 87:477-85. 2002
    ..In clinical practice, we suggest that other causes of low serum IGF-I should be excluded before applying these diagnostic criteria...
  70. ncbi request reprint Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone
    Michael I Lewis
    Division of Pulmonary Critical Care Medicine, The Burns and Allen Research Institute, Cedars Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA
    Am J Physiol Endocrinol Metab 282:E483-90. 2002
    ....
  71. ncbi request reprint Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline
    Mark E Molitch
    Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Clin Endocrinol Metab 91:1621-34. 2006
    ..The objective is to provide guidelines for the evaluation and treatment of adults with GH deficiency (GHD)...
  72. pmc IGF-I stimulates cooperative interaction between the IGF-I receptor and CSK homologous kinase that regulates SHPS-1 phosphorylation in vascular smooth muscle cells
    Yashwanth Radhakrishnan
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
    Mol Endocrinol 25:1636-49. 2011
    ..This results in the enhanced CTK transfer to SHPS-1, and the two kinases then fully phosphorylate SHPS-1, which is necessary for IGF-I stimulated cellular proliferation...

Research Grants41

  1. IGFBP5 AND INTEGRINS AND CONTROLLING IGF1 ACTIONS
    David Clemmons; Fiscal Year: 2002
    ....
  2. MECHANISMS BY WHICH IGF I STIMULATES SMOOTH MUSCLE CELLS
    David Clemmons; Fiscal Year: 2000
    ....
  3. MECHANISMS BY WHICH IGF-I STIMULATES SMOOTH MUSCLE CELLS
    David Clemmons; Fiscal Year: 2007
    ..The results may suggest novel strategies for interfering with these processes to alter the progression of atherosclerosis. ..
  4. Role of Integrins/ECM in Controlling IGF-I Actions
    David Clemmons; Fiscal Year: 2007
    ..abstract_text> ..
  5. MECHANISMS BY WHICH IGF-I STIMULATES SMOOTH MUSCLE CELLS
    David Clemmons; Fiscal Year: 2006
    ..The results may suggest novel strategies for interfering with these processes to alter the progression of atherosclerosis. ..
  6. Development of a Novel Method for Inhibiting Atherosclerosis in Diabetes
    David Clemmons; Fiscal Year: 2006
    ....
  7. ARTHEROSCLEROSIS IN INSULIN-RESISTANT, HYPERLIPIDEMIC P*
    David Clemmons; Fiscal Year: 2005
    ....
  8. CONTROL OF FIBROBLAST REPLICATION BY IGF-BINDING PROTEIN
    David Clemmons; Fiscal Year: 1993
    ....
  9. THE EFFECT OF AGING ON HORMONAL CONTROL OF REPLICATION
    David Clemmons; Fiscal Year: 1980
    ..The delineation of the factors which control somatomedin production and their alteration during the normal aging process should provide a basis for future studies into aging disorders. ..
  10. CONTROL OF FIBROBLAST REPLICATION BY IGF-I
    David Clemmons; Fiscal Year: 1991
    ..The results of these studies should provide basic information that is necessary to construct valid hypotheses regarding the role of growth factors in the response to injury and cellular aging...