Insulin-like Growth Factor and Apolipoprotein B

Ostlund, Richard E.

doi:10.1001/jama.1991.03470140049019

JAMA

1991

DOI: 10.1001/jama.1991.03470140049019

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Insulin-like Growth Factor and Apolipoprotein B

Richard E. Ostlund¹

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Cited by 3 publications

(1 citation statement)

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“…In addition, there are well-established links between IGFs and other surrogate markers for cardiovascular risk. IGF-I has been shown to correlate with LDL cholesterol in normal women (5), patients with hypothyroidism (6), and the elderly (6) and with apolipoprotein B and cardiovascular risk in normal subjects (7). There is also evidence that the IGF system is involved in the underlying pathophysiological processes associated with cardiovascular disease.…”

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confidence: 99%

Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and Hypertension in Type 2 Diabetes

et al. 2002

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The IGF system is increasingly implicated in the development of cardiovascular disease. The effects of circulating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its metabolic regulation by glucoregulatory hormones. Posttranslational phosphorylation of IGFBP-1 significantly increases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability. We have therefore examined the IGF system and IGFBP-1 phosphorylation status, using specifically developed immunoassays, in a cohort of 160 extensively characterized type 2 diabetic subjects on two occasions 12 months apart. Total IGFBP-1 (tIGFBP-1), which is predominantly highly phosphorylated, was significantly lower in subjects with known macrovascular disease triglycerides, and nonesterified fatty acids. In contrast, levels of nonphosphorylated and lesser-phosphorylated IGFBP-1 (lpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration ( ‫؍‬ 0.350, P < 0.01). tIGFBP-1 concentrations were higher in subjects treated with insulin alone (n ‫؍‬ 29) than for any other group. This effect persisted after adjustment of tIGFBP-1 levels for BMI, C-peptide, age, and sex (F ‫؍‬ 6.5, P < 0.001, ‫؍‬ ؊0.46). Such an effect was not apparent for lpIGFBP-1. We conclude that low circulating levels of hpIGFBP-1 are closely correlated with macrovascular disease and hypertension in type 2 diabetes, whereas lpIGFBP-1 isoforms are associated with glycemic control, suggesting a dual role for IGFBP-1 in the regulation of IGF actions in type 2 diabetes. Our data suggest that high circulating concentrations of highly phosphorylated IGFBP-1 may protect against the development of hypertension and cardiovascular disease by reducing the mitogenic potential of IGFs on the vasculature.

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mentioning

confidence: 99%

Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and Hypertension in Type 2 Diabetes

et al. 2002

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Basic fibroblast growth factor-induced low density lipoprotein receptor transcription and surface expression. Signal transduction pathways mediated by the bFGF receptor tyrosine kinase.

Hsu

Nicholson

Hajjar

1994

Journal of Biological Chemistry

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The Insulin-Like Growth Factor Axis and Plasma Lipid Levels in the Elderly1

Ceda

Dall’Aglio

Magnacavallo

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

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The activity of the hypothalamic-GH-insulin-like growth factor (IGF) network declines with age. It has recently been shown that increased cardiovascular mortality occurs in adults with GH deficiency. As hypercholesterolemia is common in GH-deficient adults, and because there is experimental evidence that GH may play a role in regulating plasma cholesterol, we decided to investigate the activity of the GH-IGF axis in an elderly population by measuring serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and to study their relationship with blood lipid levels. One hundred and thirty-two elderly subjects, 52 men and 80 women, were studied (age range, 60-91 yr). Men had significantly lower levels of IGFBP-3, high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) compared to the women, whereas IGF-I and IGF-II were only slightly lower. Using linear regression analysis, we observed an inverse relationship of age with IGF-I (r = -0.35; P < 0.001), IGF-II (r = 0.40; P < 0.001), IGFBP-3 (r = 0.52; P < 0.001), body mass index, and lipid levels. Univariate regression analysis showed a strong and positive correlation of both IGF-I and IGFBP-3 with HDL-C and ApoA1. Partial correlation analysis, after adjustment for age and body mass index, showed that IGFBP-3 and IGF-II were still significantly and positively related to HDL-C and ApoA1. Furthermore, a strong association was documented among IGF-I, IGF-II, and IGFBP-3. These data demonstrate that even in an elderly population, further aging is accompanied by a progressive decline in circulating IGF-I, IGF-II, and IGFBP-3, suggesting a continuing diminution of the GH-IGF axis throughout aging. Moreover, the strong correlation between HDL-C and an index of GH secretion, such as IGFBP-3, suggests that GH might play an important role in lipid metabolism in healthy elderly subjects.

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Insulin-like Growth Factor and Apolipoprotein B

Cited by 3 publications

References 12 publications

Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and Hypertension in Type 2 Diabetes

Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and Hypertension in Type 2 Diabetes

Basic fibroblast growth factor-induced low density lipoprotein receptor transcription and surface expression. Signal transduction pathways mediated by the bFGF receptor tyrosine kinase.

The Insulin-Like Growth Factor Axis and Plasma Lipid Levels in the Elderly1

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