Lewitt MS et al. (2014), The Insulin-Like Growth Factor System in Obesit...

ECB-ART-44148

J Clin Med 2014 Dec 22;34:1561-74. doi: 10.3390/jcm3041561.

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The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus.

Lewitt MS , Dent MS , Hall K .

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The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of type 2 diabetes several years later. Visceral adiposity and hepatic steatosis, along with a chronic inflammation, contribute to the IGF system phenotype in individuals with metabolic syndrome and type 2 diabetes mellitus, including changes in the normal inverse relationship between IGFBP-1 and insulin, with IGFBP-1 concentrations that are inappropriately normal or elevated. The IGF system is implicated in the vascular and other complications of these disorders and is therefore a potential therapeutic target.

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Genes referenced: LOC105438041 LOC105439578 LOC105439585

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References [+] :

Agha, Modulation of glucocorticoid metabolism by the growth hormone - IGF-1 axis. 2007, Pubmed

Agha, Modulation of glucocorticoid metabolism by the growth hormone - IGF-1 axis. 2007, Pubmed
Aydin, Three new players in energy regulation: preptin, adropin and irisin. 2014, Pubmed
Baxter, Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. 2000, Pubmed
Berryman, The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. 2013, Pubmed
Blundell, Hormone families: pancreatic hormones and homologous growth factors. 1980, Pubmed
Borai, Delta insulin-like growth factor binding protein-1 (ΔIGFBP-1): a marker of hepatic insulin resistance? 2014, Pubmed
Bredella, Effects of GH on body composition and cardiovascular risk markers in young men with abdominal obesity. 2013, Pubmed
Carmienke, General and abdominal obesity parameters and their combination in relation to mortality: a systematic review and meta-regression analysis. 2013, Pubmed
Chan, Inhibition of adipocyte differentiation by insulin-like growth factor-binding protein-3. 2009, Pubmed
Clemmons, Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes. 2012, Pubmed
Cohen, Obesity, type 2 diabetes, and cancer: the insulin and IGF connection. 2012, Pubmed
Cornford, Rapid suppression of growth hormone concentration by overeating: potential mediation by hyperinsulinemia. 2011, Pubmed
Costello, Regulation of soluble insulin-like growth factor II/mannose 6-phosphate receptor in human serum: measurement by enzyme-linked immunosorbent assay. 1999, Pubmed
Davidge-Pitts, Preferential expression of PAPPA in human preadipocytes from omental fat. 2014, Pubmed
Denley, Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. 2004, Pubmed
Desvigne, Microdialysis of insulin-like growth factor-I in human muscle. 2005, Pubmed
Djiogue, Insulin resistance and cancer: the role of insulin and IGFs. 2013, Pubmed
Dynkevich, Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive. 2013, Pubmed
Friedrich, Insulin-like growth factor I and anthropometric parameters in a Danish population. 2012, Pubmed
Frystyk, Free insulin-like growth factors in human obesity. 1995, Pubmed
Fusco, Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels. 2012, Pubmed
Gahete, Insulin and IGF-I inhibit GH synthesis and release in vitro and in vivo by separate mechanisms. 2013, Pubmed
Gallagher, Minireview: IGF, Insulin, and Cancer. 2011, Pubmed
Garten, The insulin-like growth factors in adipogenesis and obesity. 2012, Pubmed
Ginsberg, The obesity of patients with Laron Syndrome is not associated with excessive nutritional intake. 2009, Pubmed
Gleeson, Insulin-like growth factor-I response to a single bolus of growth hormone is increased in obesity. 2005, Pubmed
Gu, IGF2BP2 and IGF2 genetic effects in diabetes and diabetic nephropathy. 2012, Pubmed
Gude, The production and regulation of IGF and IGFBPs in human adipose tissue cultures. 2012, Pubmed
Guler, Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. 1989, Pubmed
Gómez, The IGF-I system component concentrations that decrease with ageing are lower in obesity in relationship to body mass index and body fat. 2004, Pubmed
Gómez-Hernández, Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the aortic vascular smooth muscle cell proliferation: role of TNF-α and IGF-II. 2013, Pubmed
Hansen, Reproduction, fat metabolism, and life span: what is the connection? 2013, Pubmed
Heald, Low insulin-like growth factor-II levels predict weight gain in normal weight subjects with type 2 diabetes. 2006, Pubmed
Hedbacker, Antidiabetic effects of IGFBP2, a leptin-regulated gene. 2010, Pubmed
Hribal, Insulin-like growth factor-I, inflammatory proteins, and fibrosis in subjects with nonalcoholic fatty liver disease. 2013, Pubmed
Hursting, Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer. 2012, Pubmed
Höybye, The growth hormone-insulin-like growth factor axis in adult patients with Prader Willi syndrome. 2003, Pubmed
Jarajapu, Protection of blood retinal barrier and systemic vasculature by insulin-like growth factor binding protein-3. 2012, Pubmed
Jeyaratnaganthan, Circulating levels of insulin-like growth factor-II/mannose-6-phosphate receptor in obesity and type 2 diabetes. 2010, Pubmed
Kong, Serum concentrations of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and cardiovascular risk factors in adolescents. 2011, Pubmed
Kotronen, Fatty liver: a novel component of the metabolic syndrome. 2008, Pubmed
Kotronen, Insulin-like growth factor binding protein 1 as a novel specific marker of hepatic insulin sensitivity. 2008, Pubmed
Kotronen, Effect of liver fat on insulin clearance. 2007, Pubmed
Kreitschmann-Andermahr, GH/IGF-I regulation in obesity--mechanisms and practical consequences in children and adults. 2010, Pubmed
Leung, Estrogen regulation of growth hormone action. 2004, Pubmed
Lewitt, Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men. 2008, Pubmed , Echinobase
Lewitt, IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women. 2010, Pubmed , Echinobase
Lewitt, Insulin-like growth factor-binding protein-1: a role in glucose counterregulation? 1991, Pubmed
Lewitt, Effect of Ghrelin on Hepatic IGF-Binding Protein-1 Production. 2013, Pubmed
Li, Insulin stimulates IGFBP-2 expression in 3T3-L1 adipocytes through the PI3K/mTOR pathway. 2012, Pubmed
Lukanova, Nonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF-binding protein-3 ratio with indices of adiposity and plasma insulin concentrations (Sweden). 2002, Pubmed
Maccario, Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity and Cushing's syndrome: indirect evaluation of sensitivity to GH. 2001, Pubmed
Mohanraj, IGFBP-3 inhibits cytokine-induced insulin resistance and early manifestations of atherosclerosis. 2013, Pubmed
Murphy, IGF2/H19 hypomethylation in a patient with very low birthweight, preocious pubarche and insulin resistance. 2012, Pubmed
Narayanan, Interactions of the IGF System with Diabetes and its Vascular Complications. 2013, Pubmed
Naukkarinen, Characterising metabolically healthy obesity in weight-discordant monozygotic twins. 2014, Pubmed
Nedić, Association between the pattern of IGFBP-1 alteration and the glucose/insulin metabolic control. 2011, Pubmed
Nedić, Posttranslational modifications of the insulin-like growth factor-binding protein 3 in patients with type 2 diabetes mellitus assessed by affinity chromatography. 2012, Pubmed
Nguyen, Human IGF binding protein-3 overexpression impairs glucose regulation in mice via an inhibition of insulin secretion. 2011, Pubmed
Petersson, Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): the Söderåkra Cardiovascular Risk Factor Study. 2009, Pubmed
Rajpathak, Insulin-like growth factor axis and risk of type 2 diabetes in women. 2012, Pubmed
Rasmussen, Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. 1995, Pubmed
Reinehr, Longitudinal association between IGFBP-1 levels and parameters of the metabolic syndrome in obese children before and after weight loss. 2011, Pubmed
Ricart, No decrease in free IGF-I with increasing insulin in obesity-related insulin resistance. 2001, Pubmed
Sabin, IGFBP-2 at the interface of growth and metabolism--implications for childhood obesity. 2011, Pubmed
Sandhu, Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. 2002, Pubmed
Sandhu, Low circulating IGF-II concentrations predict weight gain and obesity in humans. 2003, Pubmed
Savastano, Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females. 2011, Pubmed
Savastano, Beyond waist circumference in an adult male population of Southern Italy: Is there any role for subscapular skinfold thickness in the relationship between insulin-like growth factor-I system and metabolic parameters? 2012, Pubmed
Schneider, Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects. 2006, Pubmed
Siddals, IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte. 2002, Pubmed
Sirbu, Adiponectin, body mass index and hepatic steatosis are independently associated with IGF-I status in obese non-diabetic women. 2013, Pubmed
Stephens, Polymorphisms in IGF-binding protein 1 are associated with impaired renal function in type 2 diabetes. 2005, Pubmed
Street, Interactions among pro-inflammatory cytokines, IGF system and thyroid function in pre-pubertal obese subjects. 2013, Pubmed
Van Laere, A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. 2003, Pubmed
Völzke, Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample. 2009, Pubmed
Wang, Specific cleavage of insulin-like growth factor-binding protein-1 by a novel protease activity. 2006, Pubmed
Weaver, Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. 1990, Pubmed
Wheatcroft, IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis. 2009, Pubmed
Yakar, Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism. 2009, Pubmed

	Figure 1. Interaction between insulin and the insulin-like growth factor system. Inhibitory effects are shown in red and stimulatory effects, in green. GH = growth hormone; tIGF-I = total insulin-like growth factor-I (unbound and in ternary and binary complexes with IGF-binding proteins (IGFBPs)); fIGF-I = free IGF-I; EAAs = essential amino acids.
	Figure 2. Changing relationships between fasting IGFBP-1 and insulin concentrations, and bioavailable (free) IGF-I in tissues in peripheral and hepatic insulin resistance.