Genomes and Genes
insulin like growth factor binding protein 3
Summary: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
- Serin I, Tanriverdi F, Yilmaz M, Ozcelik B, Unluhizarci K. Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women. Gynecol Endocrinol. 2008;24:117-21 pubmed publisher
- Xi Y, Nakajima G, Hamil T, Fodstad O, Riker A, Ju J. Association of insulin-like growth factor binding protein-3 expression with melanoma progression. Mol Cancer Ther. 2006;5:3078-84 pubmed..These results strongly suggest that IGFBP-3 expression may be a vital cell motility, migration, and proliferation factor necessary for melanoma metastasis and is an important biomarker in human melanoma. ..
- Peeters P, Lukanova A, Allen N, Berrino F, Key T, Dossus L, et al. Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2007;14:81-90 pubmed..Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age. ..
- Baglietto L, English D, Hopper J, Morris H, Tilley W, Giles G. Circulating insulin-like growth factor-I and binding protein-3 and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:763-8 pubmed..More prospective studies are needed to clarify the age dependence of the association between IGF-I and IGFBP-3 and breast cancer. ..
- Lonn S, Inskip P, Pollak M, Weinstein S, Virtamo J, Albanes D. Glioma risk in relation to serum levels of insulin-like growth factors. Cancer Epidemiol Biomarkers Prev. 2007;16:844-6 pubmed..3; 95% confidence interval, 0.1-0.7). The results encourage future research on IGFs in relation to brain tumors in larger studies. ..
- Major J, Pollak M, Snyder K, Virtamo J, Albanes D. Insulin-like growth factors and risk of kidney cancer in men. Br J Cancer. 2010;103:132-5 pubmed publisher..Low serum IGF-I levels in this cohort of older middle-aged male smokers are associated with increased kidney cancer risk, independent of IGFBP-3. ..
- Torng P, Lee Y, Huang C, Ye J, Lin Y, Chu Y, et al. Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma. Oncogene. 2008;27:2137-47 pubmed..Our results provide evidence and indicate that IGFBP-3 plays an important role as an invasion-metastasis suppressor in ovarian EC...
- Debacq Chainiaux F, Pascal T, Boilan E, Bastin C, Bauwens E, Toussaint O. Screening of senescence-associated genes with specific DNA array reveals the role of IGFBP-3 in premature senescence of human diploid fibroblasts. Free Radic Biol Med. 2008;44:1817-32 pubmed publisher..Among these genes was IGFBP-3. Using a siRNA approach, we showed that IGFBP-3 regulates the appearance of several biomarkers of senescence after repeated exposures of WI-38 fibroblasts to tert-butylhydroperoxide and ethanol. ..
- Guix M, Faber A, Wang S, Olivares M, Song Y, Qu S, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest. 2008;118:2609-19 pubmed publisher..Moreover, combined therapeutic inhibition of EGFR and IGFIR may abrogate this acquired mechanism of drug resistance and is thus worthy of prospective clinical investigation. ..
- Takaoka M, Kim S, Okawa T, Michaylira C, Stairs D, Johnstone C, et al. IGFBP-3 regulates esophageal tumor growth through IGF-dependent and independent mechanisms. Cancer Biol Ther. 2007;6:534-40 pubmed..In aggregate, these data suggest that IGFBP-3 contributes to esophageal tumor development and progression through IGF-dependent and independent mechanisms. ..
- Williams A, Smartt H, H Zadeh A, MacFarlane M, Paraskeva C, Collard T. Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced apoptosis of human colorectal carcinoma cells through inhibition of NF-kappaB. Cell Death Differ. 2007;14:137-45 pubmed..We propose that IGFBP-3 is a non-toxic NF-kappaB inhibitor, which could be used as an adjuvant in the treatment of colon cancer. ..
- Oh S, Kim W, Kim J, Younes M, El Naggar A, Myers J, et al. Identification of insulin-like growth factor binding protein-3 as a farnesyl transferase inhibitor SCH66336-induced negative regulator of angiogenesis in head and neck squamous cell carcinoma. Clin Cancer Res. 2006;12:653-61 pubmed..These findings suggest that IGFBP-3 could be a primary target for antitumor activities of FTIs and that IGFBP-3 is an effective therapeutic approach against angiogenesis in HNSCC. ..
- Slattery M, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, et al. Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Res Treat. 2007;104:197-209 pubmed..Our data suggest that associations between insulin-related genes and breast cancer risk among women living in the Southwestern United States may be dependent on estrogen exposure and may differ by ethnicity. ..
- Rinaldi S, Peeters P, Berrino F, Dossus L, Biessy C, Olsen A, et al. IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2006;13:593-605 pubmed
- Münzer T, Rosen C, Harman S, Pabst K, St Clair C, Sorkin J, et al. Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men. Am J Physiol Endocrinol Metab. 2006;290:E1006-13 pubmed..Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined. ..
- Liu B, Lee K, Anzo M, Zhang B, Zi X, Tao Y, et al. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis. Oncogene. 2007;26:1811-9 pubmed
- Aishima S, Basaki Y, Oda Y, Kuroda Y, Nishihara Y, Taguchi K, et al. High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma. Cancer Sci. 2006;97:1182-90 pubmed..Low expression of IGFBP-3 was independently associated with poor survival. IGFBP-3 could be a molecular target of intrinsic importance for further development of novel therapeutic strategy against HCC. ..
- Han J, Choi B, Choi J, Lee S, Ju S. The prognostic significance of pretreatment plasma levels of insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein-3 in patients with advanced non-small cell lung cancer. Lung Cancer. 2006;54:227-34 pubmed..High plasma levels of IGF-1, IGF-2, and IGFBP-3 were associated with good prognosis in patients with advanced NSCLC. Further validation of these results is needed to determine the prognostic significance of IGF system in advanced NSCLC. ..
- Santer F, Bacher N, Moser B, Morandell D, Ressler S, Firth S, et al. Nuclear insulin-like growth factor binding protein-3 induces apoptosis and is targeted to ubiquitin/proteasome-dependent proteolysis. Cancer Res. 2006;66:3024-33 pubmed..Moreover, we show that IGFBP-3, if ectopically expressed in the nucleus, can induce apoptotic cell death. These results suggest that ubiquitin/proteasome-mediated proteolysis of IGFBP-3 may contribute to down-regulation of apoptosis. ..
- Jenkins P, Khalaf S, Ogunkolade W, McCarthy K, David T, Hands R, et al. Differential expression of IGF-binding protein-3 in normal and malignant colon and its influence on apoptosis. Endocr Relat Cancer. 2005;12:891-901 pubmed..These effects are mediated in part by the PI-3K pathway in contrast to the MAP kinase pathway used by IGF-I. ..
- Ahn J, Weinstein S, Snyder K, Pollak M, Virtamo J, Albanes D. No association between serum insulin-like growth factor (IGF)-I, IGF-binding protein-3, and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2006;15:2010-2 pubmed
- Serrano M, Romero A, Cendales R, Sanchez Gomez M, Bravo M. Serum levels of insulin-like growth factor-I and -II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer. Biomedica. 2006;26:258-68 pubmed..07-0.73]) lower risk of cervical cancer, respectively, compared with women in the corresponding reference category. These data suggest that low values of IGF-I and IGF-I:IGFBP-3 molar ratio may be associated with cervical cancer. ..
- Jerome L, Alami N, Belanger S, Page V, Yu Q, Paterson J, et al. Recombinant human insulin-like growth factor binding protein 3 inhibits growth of human epidermal growth factor receptor-2-overexpressing breast tumors and potentiates herceptin activity in vivo. Cancer Res. 2006;66:7245-52 pubmed..These results emphasize the merit of evaluating simultaneous blockade of the HER-2 and IGF-IR pathways using combination therapy with rhIGFBP-3 plus Herceptin in human clinical trials of patients with HER-2-positive breast cancer. ..
- Flanagan D, Holt R, Owens P, Cockington R, Moore V, Robinson J, et al. Gender differences in the insulin-like growth factor axis response to a glucose load. Acta Physiol (Oxf). 2006;187:371-8 pubmed..321, P = 0.004) and IGF-I (r = 0.339 P = 0.002) in men but not women. Our data show that IGFBP-1, IGFBP-3 and IGF-I show acute changes following a glucose load and there are marked gender differences in these responses. ..
- Chang Y, Cho J, Cho H, Kim H, Chang J, Ahn C, et al. 9-cis retinoic acid induces insulin-like growth factor binding protein-3 through DR-8 retinoic acid responsive elements. Cancer Biol Ther. 2006;5:586-92 pubmed..IGFBP-3 gene expression by 9cRA is mediated by a distinct DR-8 RARE located in the proximal region of the IGFBP promoter and involves the RAR-beta, a putative tumor suppressor in NSCLC. ..
- Canzian F, McKay J, Cleveland R, Dossus L, Biessy C, Rinaldi S, et al. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study. Br J Cancer. 2006;94:299-307 pubmed..Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians. ..
- Burrows C, Holly J, Laurence N, Vernon E, Carter J, Clark M, et al. Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes. Endocrinology. 2006;147:3484-500 pubmed..In summary, with three breast epithelial cell lines, IGFBP-3 had positive or negative effects on growth and survival dependent upon the status of cholesterol-stabilized integrin receptor complexes. ..
- Gram I, Norat T, Rinaldi S, Dossus L, Lukanova A, Tehard B, et al. Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women. Int J Obes (Lond). 2006;30:1623-31 pubmed..Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity. ..
- Morimoto L, Newcomb P, White E, Bigler J, Potter J. Variation in plasma insulin-like growth factor-1 and insulin-like growth factor binding protein-3: personal and lifestyle factors (United States). Cancer Causes Control. 2005;16:917-27 pubmed..Only age was significantly related to circulating IGFBP-3. Although the sources of inter-individual variation of IGF-1 and IGFB-3 are not yet fully understood, this analysis provides some insights into factors that may contribute. ..
- Mostyn A, Sebert S, Litten J, Perkins K, Laws J, Symonds M, et al. Influence of porcine genotype on the abundance of thyroid hormones and leptin in sow milk and its impact on growth, metabolism and expression of key adipose tissue genes in offspring. J Endocrinol. 2006;190:631-9 pubmed
- Cobb L, Liu B, Lee K, Cohen P. Phosphorylation by DNA-dependent protein kinase is critical for apoptosis induction by insulin-like growth factor binding protein-3. Cancer Res. 2006;66:10878-84 pubmed..These studies reveal a novel regulatory mechanism for the actions of IGFBP-3 in prostate cancer and show phosphorylation of Ser(156) to be functionally critical in its apoptosis-inducing actions. ..
- Tomii K, Tsukuda K, Toyooka S, Dote H, Hanafusa T, Asano H, et al. Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers. Int J Cancer. 2007;120:566-73 pubmed..079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined. ..
- Bhattacharyya N, Pechhold K, Shahjee H, Zappala G, Elbi C, Raaka B, et al. Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus. J Biol Chem. 2006;281:24588-601 pubmed..These results indicate that IGFBP-3 can induce apoptosis in an IGF-independent manner without being secreted or concentrated in the nucleus. ..
- Liao L, Dearth R, Zhou S, Britton O, Lee A, Xu J. Liver-specific overexpression of the insulin-like growth factor-I enhances somatic growth and partially prevents the effects of growth hormone deficiency. Endocrinology. 2006;147:3877-88 pubmed..Higher circulating levels of IGF-I can stimulate somatic growth and lean mass and improve glucose tolerance. ..
- Wiley A, Katsaros D, Fracchioli S, Yu H. Methylation of the insulin-like growth factor binding protein-3 gene and prognosis of epithelial ovarian cancer. Int J Gynecol Cancer. 2006;16:210-8 pubmed..These results suggest that IGFBP-3 promoter methylation may be a useful prognostic marker for disease progression and death in early-stage ovarian cancer. ..
- Gleeson H, Shalet S. GH responsiveness varies during the menstrual cycle. Eur J Endocrinol. 2005;153:775-9 pubmed..This may have clinical implications for women with isolated GH deficiency with regular menstrual cycles on a fixed dose of GH. This possibility requires further study. ..
- Slattery M, Baumgartner K, Byers T, Guiliano A, Sweeney C, Herrick J, et al. Genetic, anthropometric, and lifestyle factors associated with IGF-1 and IGFBP-3 levels in Hispanic and non-Hispanic white women. Cancer Causes Control. 2005;16:1147-57 pubmed..These differences could be due to the combined effects of genetic and behavioral factors which could account for ethnic differences in the risk of breast cancer and other chronic diseases. ..
- Oh S, Lee O, Schroeder C, Oh Y, Ke S, Cha H, et al. Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor-independent urokinase-type plasminogen activator inhibition. Mol Cancer Ther. 2006;5:2685-95 pubmed..Our findings indicate that IGFBP-3 may be a promising anti-invasive and antimetastatic therapeutic agent in lung cancer. ..
- Renehan A, Harvie M, Howell A. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on. Endocr Relat Cancer. 2006;13:273-8 pubmed..The reasons are complex and include differences in study design, lack of standardisation between assays, and variations in IGFBP-3 proteolytic activity--these are discussed in this commentary. ..
- Zhigang Z, Jieming L, Su L, Wenlu S. Serum insulin-like growth factor I/free prostate specific antigen (IGF-I/fPSA) ratio enhances prostate cancer detection in men with total PSA 4.0-10.0 ng/ml. J Surg Oncol. 2007;96:54-61 pubmed..Our data show that IGF-I/fPSA as a promising marker can enhance PCa detection in ambiguous cases often found in the tPSA between 4.0 and 10.0 ng/ml. ..
- Reynaud K, Chastant Maillard S, Batard S, Thoumire S, Monget P. IGF system and ovarian folliculogenesis in dog breeds of various sizes: is there a link?. J Endocrinol. 2010;206:85-92 pubmed publisher..These differences were associated with significant differences in some functional aspects of ovarian follicles...
- Zhang L, Gardiner B, Smith D, Pivonka P, Grodzinsky A. On the role of diffusible binding partners in modulating the transport and concentration of proteins in tissues. J Theor Biol. 2010;263:20-9 pubmed publisher..As the increase in free protein is 'tunable' by cells, our analyses are postulated to demonstrate a general regulatory principle that may operate in any tissues throughout the body. ..
- Haghshenas Z, Sotoudeh K, Karamifar H, Karamizadeh Z, Amirhakimi G. The role of insulin like growth factor (IGF)-1 and IGF-binding protein-3 in diagnosis of Growth Hormone Deficiency in short stature children. Indian J Pediatr. 2009;76:699-703 pubmed publisher..No correlations were found between GH level and serum levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of those tests in assessment of GHD were poor. ..
- Ueki I, Giesy S, Harvatine K, Kim J, Boisclair Y. The acid-labile subunit is required for full effects of exogenous growth hormone on growth and carbohydrate metabolism. Endocrinology. 2009;150:3145-52 pubmed publisher..Overall, these results suggest that the GH effects mediated by endocrine IGF-I depends on ALS, and accordingly null ALS mice are less responsive to exogenous GH therapy. ..
- Gunter M, Hoover D, Yu H, Wassertheil Smoller S, Manson J, Li J, et al. A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:921-9 pubmed publisher..Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data. ..
- Li N, Zhou L, Zhang B, Dong P, Lin W, Wang H, et al. Recombinant human growth hormone increases albumin and prolongs survival in patients with chronic liver failure: a pilot open, randomized, and controlled clinical trial. Dig Liver Dis. 2008;40:554-9 pubmed publisher..rhGH replacement therapy increased albumin and tended to improve survival in adult patients with chronic liver failure. ..
- Shahjee H, Bhattacharyya N, Zappala G, Wiench M, Prakash S, Rechler M. An N-terminal fragment of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in human prostate cancer cells in an IGF-independent manner. Growth Horm IGF Res. 2008;18:188-97 pubmed..The N-terminal 1-97-IGFBP-3 fragment induces apoptosis in human prostate cancer cells in an IGF-independent manner. Generation of the fragment might contribute to the proapoptotic activity of IGFBP-3 in vivo. ..
- Vidergor G, Goldfarb A, Glaser B, Dresner Pollak R. Growth hormone reserve in adult beta thalassemia patients. Endocrine. 2007;31:33-7 pubmed..The clinical benefits of GH therapy need to be determined. GHD alone does not account for the high prevalence of reduced IGF-1 in adult beta-thalassemia. ..
- Akanji A, Ohaeri J, Al Shammri S, Fatania H. Associations of blood levels of insulin-like growth factor (IGF)-I, IGF-II and IGF binding protein (IGFBP)-3 in schizophrenic Arab subjects. Clin Chem Lab Med. 2007;45:1229-31 pubmed..These results demonstrate that IGF-II levels are increased in patients with SZ and show significant associations with atherogenic lipoproteins. We suggest a possible link between IGF-II metabolism and atherogenesis in SZ. ..
- Keller A, Wu Z, Kratzsch J, Keller E, Blum W, Kniess A, et al. Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration. Eur J Endocrinol. 2007;156:647-53 pubmed..These differences need to be considered for therapeutic use and for detection of rhGH doping. ..
- Ormsbee M, Clapper J, Clapper J, Vukovich M. The impact of varying dietary protein on serum IGF-I, IGFBP-1, and IGFBP-3 during 6 days of physical activity. Int J Sport Nutr Exerc Metab. 2007;17:127-39 pubmed..A 6-d modification of protein intake, while in energy balance, during a strength and conditioning program does not appear to modify serum concentrations of IGF-I or IGFBP-1 or relative amounts of IGFBP-3. ..
- Flood A, Mai V, Pfeiffer R, Kahle L, Remaley A, Rosen C, et al. The effects of a high-fruit and -vegetable, high-fiber, low-fat dietary intervention on serum concentrations of insulin, glucose, IGF-I and IGFBP-3. Eur J Clin Nutr. 2008;62:186-96 pubmed
- Seitz C, Djavan B. [Biological markers of prostate cancer]. Ann Urol (Paris). 2006;40:329-35 pubmed..Therefore, there is a need for new instruments likely to improve the specificity of blood PSA levels between 4.0 and 10 ng/mL and the screening for prostate cancer in subjects with low PSA. Recent data are reviewed. ..
- Daniels K, Hill S, Knowlton K, James R, McGilliard M, Akers R. Effects of milk replacer composition on selected blood metabolites and hormones in preweaned Holstein heifers. J Dairy Sci. 2008;91:2628-40 pubmed publisher..It is likely that the diets used in this study were not diverse enough in composition to elicit such changes or that the efficiency of use of absorbed protein and fat was not different in these animals. ..
- Paulo R, Brundage R, Cosma M, Mielke K, Bowers C, Veldhuis J. Estrogen elevates the peak overnight production rate of acylated ghrelin. J Clin Endocrinol Metab. 2008;93:4440-7 pubmed publisher..9+/-0.2 (no E2) ng/kg.min (P=0.039). Acylated ghrelin has a multifold larger distribution volume and MCR than total ghrelin. An estrogenic milieu augments synthesis and/or acylation of ghrelin peptide without altering its MCR. ..
- Yu J, Warycha M, Christos P, Darvishian F, Yee H, Kaminio H, et al. Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients. J Transl Med. 2008;6:70 pubmed publisher..Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients. ..
- Valūniene M, Danylaite A, Kryziūte D, Ramanauskaite G, Lasiene D, Lasas L, et al. [Postnatal growth in children born small and appropriate for gestational age during the first years of life]. Medicina (Kaunas). 2009;45:51-60 pubmed..A greater catch-up in body mass index and tendency towards central pattern of fat distribution during the first years of life might be predisposing factors for the development of long-term metabolic complications in these individuals. ..
- Jiang Y, Steinle J. Systemic propranolol reduces b-wave amplitude in the ERG and increases IGF-1 receptor phosphorylation in rat retina. Invest Ophthalmol Vis Sci. 2010;51:2730-5 pubmed publisher..Systemic application of beta-adrenergic receptor antagonists may have detrimental effects on the retina. ..
- Friedrich N, Aumann N, Dorr M, Felix S, Nauck M, Wallaschofski H, et al. Lack of association between insulin-like growth factor-1 or insulin-like growth factor-binding protein-3 and left ventricular hypertrophy: results of the Study of Health in Pomerania. J Hypertens. 2010;28:856-64 pubmed publisher..No such relation became apparent in men. No association between IGF-I levels and LVH was found. Potential hypertrophic effects of free serum IGF-I levels might be mediated by lower IGFBP-3 levels. ..
- Rao M, Mulligan K, Tai V, Wen M, Dyachenko A, Weinberg M, et al. Effects of insulin-like growth factor (IGF)-I/IGF-binding protein-3 treatment on glucose metabolism and fat distribution in human immunodeficiency virus-infected patients with abdominal obesity and insulin resistance. J Clin Endocrinol Metab. 2010;95:4361-6 pubmed publisher..Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals...