Insulin, insulin-like growth factors, and vascular endothelium

Bar, Robert S.; Boes, Mary; Dake, Brian L.; Booth, Barbara A.; Henley, Sherry A.; Sandra, Alexander

doi:10.1016/0002-9343(88)90398-1

Cited by 113 publications

(59 citation statements)

References 33 publications

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“…After poration the cells were exposed to 5 mM glucose with or without 5 mM glucosamine for 3 atherogenesis. TGFa is normally found in arterioles (4) and is mitogenic for the arterial endothelium (18) (26), that do exhibit biologic activities toward vascular cells (27). Insulin did not, however, affect the transcription of TGFa in the aortic smooth muscle cells.…”

Section: Discussionmentioning

confidence: 88%

Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

McClain

Paterson

Roos

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

178

110

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We have investigated the regulation of the expression of two growth factors found in vascular smooth muscle, transforming growth factor a (TGFa) and basic fibroblast growth factor (bFGF). Cells cultured in medium containing 30 mM glucose exhibited a 2-fold increase in TGFa mRNA and a 3-fold increase in bFGF mRNA compared with cells grown in normal (5.5 mM) glucose. Glucosamine was more potent than glucose, leading to a 6-fold increase in TGFa mRNA. TGFa protein levels were also increased by glucosamine treatment, and the predominant species present was the membrane-bound precursor form of TGFa. To examine further the regulation of growth factors by sugars, cultured rat aortic smooth muscle cells were transfected with a plasmid construct consisting of a 1.2-kilobase-pair fragment of the TGFa promoter linked to a luciferase reporter gene. Increasing the concentration ofglucose in the culture medium from 5.5 mM to 30 mM led to a rapid, 1.7-fold increase in the activity of the TGFa promoter. Glucosamine was much more potent than glucose in this stimulation, with 2 mM gluamine causing a 12-fold increase in TGFa promoter activity. Insulin had no effect on luciferase activity in either the presence or the absence of added sugars. The glucose response element of the TGFa gene maps to a 130-base-pair segment that includes three potential binding sites for the transcription factor Spl. We conclude that high glucose concentrations such as are reached in diabetes mellitus can stimulate the transcription of the genes for growth factors in vascular smooth muscle cells. This signaling pathway apparently involves the metabolism of glucose to glucosamine. This effect could be representative of nutritional regulation of a family of genes and could contribute to the toxicity of hyperglycemia and the vascular complications of diabetes.Vascular smooth muscle cell proliferation is an early event in the pathogenesis of atherosclerosis, and growth factors have been hypothesized to play an important role in the control of this process (1). For example, platelet-derived growth factor is expressed in atherosclerotic lesions and is found in macrophages in all phases ofthe development of those lesions (2). Growth factors synthesized by the vascular smooth muscle cells themselves may also be involved in the pathogenesis of vascular disease. Thus, the exposure of vascular smooth muscle cells to growth factors could be determined by the plasma concentration of a growth factor, by delivery from blood-derived cells, or by the production rate of the growth factor by cells within the vessel wall. To examine whether the synthesis of growth factors might be sensitive to environmental conditions, we studied two growth factors known to be expressed in vascular smooth muscle cells, transforming growth factor a (TGFa; refs. 3 and 4) and basic fibroblast growth factor (bFGF; refs. 5 and 6). In addition, because the promoter for the TGFa gene has been cloned and characterized (7, 8), we studied in more detail the transcriptional regulation of the ...

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Section: Discussionmentioning

confidence: 88%

Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

McClain

Paterson

Roos

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

178

110

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“…However, because of the intrinsic propriety of the molecule, one could speculate that increased expression of PSA-NCAM at the surface of ␤-cells could influence contacts between ␤-cells and other islet cells. This result could facilitate secretion of insulin into the circulation from ␤-cells able to establish connections with capillaries (19). In insulin granules, PSA-NCAM may contribute to cation storage (in particular Mg 2+ ) because of the electronegativity of the molecule necessary for convertase action (20).…”

Section: Discussionmentioning

confidence: 99%

Sialylated form of the neural cell adhesion molecule (NCAM): a new tool for the identification and sorting of beta-cell subpopulations with different functional activity.

et al. 2001

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To clarify the relationship between variations in ␤-cell mass and pancreatic function, we investigated the possibility to analyze, quantify, and sort ␤-cell subpopulations with different functional maturity. To this aim, we tested the reliability of the sialylated form of neural cell adhesion molecule (NCAM) (PSA-NCAM) as a marker of ␤-cell functional activity. Islet cells isolated from adult rats were analyzed for their PSA-NCAM abundance using an anti-PSA-NCAM antibody. We found that PSA-NCAM is expressed only in ␤-cells. The PSA-NCAM labeling was also studied with a fluorescenceactivated cell sorter. We showed that the ␤-cell population is heterogeneous for PSA-NCAM labeling. To directly determine the relationship between PSA-NCAM labeling and ␤-cell activity, in vitro insulin secretion studies were performed on sorted ␤-cell subpopulations using a perifusion technique. Two ␤-cell subpopulations were analyzed: one that was highly labeled for PSA-NCAM and another that was poorly labeled. Insulin secretion from high PSA-NCAMlabeled ␤-cells was significantly higher than that in low PSA-NCAM-labeled ␤-cells. This differential expression in the ␤-cell population was well correlated with differences in glucose responsiveness. PSA-NCAM seems thus suitable for use as a tool to identify ␤-cell subpopulations according to their glucose responsiveness. Diabetes 50 (Suppl. 1):S125-S130, 2001

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“…7 The serum free IGF-I levels in our study lie within the same range as previously reported for the molecular affinity of the IGF-I receptor on both vascular endothelium and vascular smooth muscle cells. 3,30 Because endothelial cells are continuously exposed to IGF-I in vivo, it is conceivable that endocrine IGF-I might be of importance in both the normal physiology of vascular endothelium and in disease states, eg, atherosclerosis. 31 Evidence exists that IGF-I does cross vascular endothelium and in this respect might be also comparable to insulin.…”

Section: Discussionmentioning

confidence: 99%

“…31 Evidence exists that IGF-I does cross vascular endothelium and in this respect might be also comparable to insulin. 30,32 The importance of circulating (endocrine) IGF-I has been challenged by the autocrine/ paracrine concept of IGF-I since most cells implicated in the pathogenesis of atherosclerosis are capable of expressing (autocrine and paracrine) IGF-I, IGF-I receptors, and IGFBPs. wall is independent of pituitary growth hormone secretion 33 and that endothelial denudation of blood vessels in rats increases the accumulation of IGF-I in vascular smooth muscles without concomitant changes in hepatic IGF-I mRNA expression and serum total IGF-I levels.…”

Section: Discussionmentioning

confidence: 99%

Serum Total IGF-I, Free IGF-I, and IGFBP-1 Levels in an Elderly Population

Janssen

Stolk

Pols

et al. 1998

ATVB

221

148

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Abstract-Recently, a method to measure free insulin-like growth factor-I (IGF-I) levels has been developed. Free IGF-I levels may have greater physiological and clinical relevance than total (bound and free) IGF-I. The associations between the circulating IGF-I/IGF binding protein (IGFBP) system and cardiovascular disorders was studied. In a cross-sectional study of 218 healthy persons (103 men, 115 women) aged 55 to 80 years, fasting serum (total and free) IGF-I and IGFBP-1 levels, lipid profile, insulin, and glucose were measured. In addition, blood pressure, body mass index (BMI), and waist-hip ratio (WHR) were measured. Ultrasonography of both carotid arteries was performed to investigate the presence of atherosclerotic lesions. A history of angina pectoris, the presence of a possible or definite myocardial infarction on the ECG, and plaques in the carotid arteries were used as indicators of presence of cardiovascular signs and symptoms. Free IGF-I was inversely related to serum triglycerides (Pϭ.04, adjusted for age and sex). Mean free IGF-I levels in subjects without signs or symptoms of cardiovascular diseases were significantly higher than in those with at least one cardiovascular symptom or sign (Pϭ.002, adjusted for age and sex). Free IGF-I levels were also higher in subjects who had no atherosclerotic plaques in the carotid arteries (Pϭ.02, adjusted for age and sex) and who had never smoked (Pϭ.02, adjusted for age and sex). IGFBP-1 showed an inverse relation with insulin, BMI, and WHR and a positive relation with HDL cholesterol. The associations between IGFBP-1 levels and HDL cholesterol, WHR, and BMI remained significant after adjustment for fasting insulin levels. High fasting serum free IGF-I levels are associated with a decreased presence of atherosclerotic plaques and coronary artery disease and lower serum triglycerides, whereas high fasting IGFBP-1 levels are associated with a more favorable cardiovascular risk profile. The findings suggest that the IGF-I/IGFBP system is related to cardiovascular risk factors and atherosclerosis. (Arterioscler Thromb Vasc Biol. 1998;18:277-282.)

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Insulin, insulin-like growth factors, and vascular endothelium

Cited by 113 publications

References 33 publications

Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

Sialylated form of the neural cell adhesion molecule (NCAM): a new tool for the identification and sorting of beta-cell subpopulations with different functional activity.

Serum Total IGF-I, Free IGF-I, and IGFBP-1 Levels in an Elderly Population

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