The role of insulin‐like growth factor‐I and its binding proteins in glucose homeostasis and type 2 diabetes

Rajpathak, Swapnil; Gunter, Marc J.; Wylie‐Rosett, Judith; Ho, Gloria Y.F.; Kaplan, Robert C.; Muzumdar, Radhika; Rohan, Thomas E.; Strickler, Howard D.

doi:10.1002/dmrr.919

Cited by 224 publications

(185 citation statements)

References 172 publications

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“…Individually, the different components of the metabolic syndrome have most often been shown to be associated with low IGF1 values (27,28,29,30,31,32,33). In this study, when investigated as dichotomous variables, only the component of high triglycerides was associated with IGF1 concentrations.…”

Section: Discussionmentioning

confidence: 61%

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Bunderen

Oosterwerff

Schoor

et al. 2013

European Journal of Endocrinology

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Objective: High as well as low levels of IGF1 have been associated with cardiovascular diseases (CVD). The relationship of IGF1 with (components of) the metabolic syndrome could help to clarify this controversy. The aims of this study were: i) to investigate the association of IGF1 concentration with prevalent (components of) the metabolic syndrome; and ii) to examine the role of (components of) the metabolic syndrome in the relationship between IGF1 and incident CVD during 11 years of follow-up. Methods: Data were used from the Longitudinal Aging Study Amsterdam, a cohort study in a representative sample of the Dutch older population (R65 years). Data were available in 1258 subjects. Metabolic syndrome was determined using the definition of the US National Cholesterol Education Program Adult Treatment Panel III. CVD were ascertained by self-reports and mortality data. Results: Levels of IGF1 in the fourth quintile were associated with prevalent metabolic syndrome compared with the lowest quintile (odds ratio: 1.59, 95% confidence interval (CI) 1.09-2.33). The middle up to the highest quintile of IGF1 was positively associated with high triglycerides in women. Metabolic syndrome was not a mediator in the U-shaped relationship of IGF1 with CVD. Both subjects without the metabolic syndrome and low IGF1 levels (hazard ratio (HR) 1.75, 95% CI 1.12-2.71) and subjects with the metabolic syndrome and high IGF1 levels (HR 2.28, 95% CI 1.21-4.28) demonstrated increased risks of CVD. Conclusions: In older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Furthermore, this study suggests the presence of different pathomechanisms for both low and high IGF1 levels and incident CVD.

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Section: Discussionmentioning

confidence: 61%

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Bunderen

Oosterwerff

Schoor

et al. 2013

European Journal of Endocrinology

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“…The IGF-1R is commonly overexpressed in many cancers, including NSCLC, and IGF-1 and IGF-2 link to IGF-1R leading the consequent activation of intracellular signaling pathways, then affecting cancer cell proliferation, adhesion, migration and are critical for cancer cell survival and metastases (LeRoith et al, 2003). What's more, the insulin-like effects of IGF-1 via IGF-1R played a crucial part in the maintenance of normal glucose homeostasis and may contribute to the etiopathogenesis of type 2 diabetes (Rajpathak et al, 2009). In our study, higher IGF-1R expression was found in NSCLC with preDM, which is supported by previous study reported by Rosalyn Ferguson whose study found that, in conditions of hyperinsulinemia, there was the higher phosphorylation of IR/IGF-1R which contributed to the increased growth of mammary tumors (Ferguson et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Expression Characteristics of Proteins of the Insulin-like Growth Factor Axis in Non-small Cell Lung Cancer Patients with Preexisting Type 2 Diabetes Mellitus

Jing¹,

Tang²,

Chen³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

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“…The biology of the IGF system is complex, consisting of ligands (IGF-I and IGF-II) and the cognate receptors (IGF-IR and IGF-IIR) in addition to six IGF-binding proteins (IGFBPs), and plays an important role in cell growth and proliferation [13,14]. IGF-I shares structural homology with insulin and, like insulin, promotes the peripheral uptake of glucose and fatty acids [15].…”

Section: Igf Systemmentioning

confidence: 99%

The Impact of Neutrophil Proteinase 3 on IGFBP-3 Proteolysis in Obesity

Robins¹,

Oh²

2014

Intern Med

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Obesity is a complex disorder and is a major risk factor associated with the incidence of insulin resistance (IR), diabetes, cardiovascular disease (CVD) and other metabolic disorders. The endocrine paradigm suggests that visceral fat in obesity, consisting primarily of adipocytes, secretes various pro-inflammatory adipokines such as tumor necrosis factor (TNF), leptin, visfatin, resistin, and IL-6 creating a state of local inflammation further resulting in chronic systemic inflammation and accelerating the events leading to systemic IR, diabetes and metabolic syndrome.The insulin-like growth factor (IGF) system plays a major role in growth, development and maintenance of homeostasis in normal cells. IGF binding protein-3 (IGFBP-3), the major binding protein in circulation, has been shown to be associated with obesity, IR, type II diabetes mellitus (T2DM) and CVD. Recent studies have demonstrated the IGFBP-3-specific receptor (IGFBP-3R) is a novel protein mediating the anti-inflammatory function of IGFBP-3. IGFBP-3 inhibits adipokine-induced insulin resistance and early manifestations of atherosclerosis via inhibition of NF-κB signaling in adipocytes.Furthermore, decreases in total IGFBP-3 levels and increases in proteolyzed IGFBP-3 in circulation have been documented in obese populations compared to their normal counterparts further establishing a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as IR. Conversely, our recent studies have identified that neutrophil serine protease (NSP) PR3, an IGFBP-3 specific protease in obesity, is positively correlated with IGFBP-3 proteolysis, IR, body mass index, TNF and IL-8. These findings strongly suggest that obesity-induced activation of PR3 abrogates the anti-inflammatory, insulin-sensitizing IGFBP-3/IGFBP-3R cascade, resulting in IR and its progression to T2DM. The complete characterization of the underlying mechanism and functional significance of the PR3-IGFBP-3/IGFBP-3R cascade in obesity will foster identification of the diagnostic and therapeutic potential of PR3 inhibition in insulin resistance and its sequelae.

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The role of insulin‐like growth factor‐I and its binding proteins in glucose homeostasis and type 2 diabetes

Cited by 224 publications

References 172 publications

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Expression Characteristics of Proteins of the Insulin-like Growth Factor Axis in Non-small Cell Lung Cancer Patients with Preexisting Type 2 Diabetes Mellitus

The Impact of Neutrophil Proteinase 3 on IGFBP-3 Proteolysis in Obesity

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