Production of hyaluronan and chondroitin sulphate proteoglycans from human arterial smooth muscle--the effect of glucose, insulin, IGF-I or growth hormone

Erikstrup, Christian; Pedersen, Lene-Marie; Heickendorff, Lene; Ledet, Thomas; Rasmussen, Lars Melholt

doi:10.1530/eje.0.1450193

Cited by 39 publications

(31 citation statements)

References 34 publications

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“…Thus, TNF-a (2), interleukin-1 (IL-1) (9), IL-4 (10), and peroxisome proliferatoractivated receptor (PPAR) agonists (11) upregulate the synthesis, and interestingly insulin decreases the production (2). This direct effect of insulin on vascular cells is in agreement with other insulin effects concerning both NO synthesis, vasomotoric response (12), expression of adhesion molecules (13), matrix synthesis (14,15), and calcifications (16,17). The understanding of insulin effects in vascular cells is important, since it is not known whether hyperinsulinism or lack of insulin effects in some pathways are prevailing in type 2 diabetes (18,19).…”

Section: Introductionsupporting

confidence: 76%

“…From this position, OPG can be competitively washed into the circulation by heparin (6). Since insulin may alter proteoglycan composition (14,15,40) it is possible that the observed effects of insulin could be explained by altered binding to surface proteoglycans. In addition to alterations in synthesis and releasability from vascular surfaces, it is also theoretically possible that the degradation of plasma OPG may partly explain the observed effects of insulin.…”

Section: Discussionmentioning

confidence: 99%

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Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Jörgensen

Vind²,

Nybo³

et al. 2009

European Journal of Endocrinology

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Objective: Osteoprotegerin (OPG) is a soluble tumour necrosis factor-receptor-like molecule present in connective tissues, especially bone and vasculature. It is known to accumulate in the arterial wall in diabetes. As its synthesis in vascular cells is decreased by insulin, we wanted to elucidate the acute effects of insulin on plasma OPG concentrations in individuals with type 2 diabetes and obese individuals compared with lean controls. Design: The study population consisted of ten type 2 diabetic, ten obese subjects, and ten lean subjects with no family history of diabetes. Methods: All subjects underwent a 4-h euglycemic-hyperinsulinemic clamp. Plasma OPG, insulin, lactate, HbA1c, cholesterol, triglycerides, free fatty acids (FFA), and glucose disposal rate were measured before and at the end of the clamp. Results: Baseline OPG concentrations did not differ significantly between groups. Insulin infusion decreased plasma OPG concentrations in all groups (P!0.01); however, the fall in OPG was 50% less in obese and type 2 diabetic individuals (PZ0.007). Baseline OPG correlated with fasting insulin, baseline lactate, and low density lipoprotein cholesterol in the diabetic group, and with baseline FFA in the lean group. The relative change of OPG in response to insulin correlated inversely with HbA1c and baseline FFA in the lean group. Conclusions: Acute hyperinsulinemia decreases plasma OPG, but with diminished effect in individuals with type 2 diabetes and obesity. Increased levels of OPG in arteries and plasma in diabetes together with the capability of plasma OPG as a cardiovascular risk predictor may be related to the described effects of insulin.European Journal of Endocrinology 161 95-101

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Section: Introductionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Jörgensen

Vind²,

Nybo³

et al. 2009

European Journal of Endocrinology

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“…Finally, exposure to high glucose concentrations also increases hyaluronan synthesis in renal proximal tubular cells (15), in renal interstitial fibroblasts (16), and in vascular smooth muscle cells (17). Thus, the broader implications of this model for diabetic pathology become clearer.…”

Section: Figmentioning

confidence: 94%

“…Previous studies have shown increased hyaluronan content in glomeruli isolated from diabetic animals (13) and in mesangial cells cultured in medium with a high glucose concentration (14). Exposure to high glucose concentrations also increases hyaluronan synthesis in renal proximal tubular cells (15), in renal interstitial fibroblasts (16), and in vascular smooth muscle cells (17), all of which are involved in normal kidney physiology.…”

mentioning

confidence: 93%

Hyaluronan Structures Synthesized by Rat Mesangial Cells in Response to Hyperglycemia Induce Monocyte Adhesion

Ai-min

Hascall

2004

Journal of Biological Chemistry

128

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Mesangial expansion, the principal glomerular lesion in diabetic nephropathy, is preceded by a phenotypic activation and transient proliferation of the glomerular mesangial cells and by a prominent glomerular infiltration of monocytes and macrophages. Because this infiltration seems to play a key role in the subsequent mesangial matrix expansion, we tested the response of cultures of rat mesangial cells (RMCs) for monocyte adhesion in response to hyperglycemia. Increasing the medium glucose concentration from 5.6 mM (normal) to 25.6 mM (hyperglycemic) significantly increased hyaluronan in the cell matrix, with a concurrent 3-to 4-fold increase in adhesion of U937 monocytic leukemic cells to cultures of near confluent RMCs. These responses were attributed directly to the high glucose concentration and not to increased extracellular osmolality. The monocytes primarily bind directly to hyaluronan-based structures in vitro. Abnormal deposits of hyaluronan were found in glomeruli of kidney sections from diabetic rats 1 week after streptozotocin treatment, often with closely associated monocytes/macrophages, suggesting that similar structures are relevant in vivo. The monocyte adhesion response to high glucose concentration required growth stimulation of RMCs by serum and activation of protein kinase C, and was inhibited by prior passage of the RMCs in the presence of heparin. These results suggest that the response may be cell growth state and protein kinase C-dependent. When incubated with the viral mimetic, poly I:C, in the presence of normal glucose, heparin-passaged RMCs still increased cell-associated hyaluronan and exhibited hyaluronan-mediated adhesion of monocytes, indicating that the two stimuli, high glucose and viral mimetic, induce the production of the hyaluronan structures that promote monocyte adhesion by distinctly different intracellular signaling mechanisms.Mesangial expansion, the principal glomerular lesion in diabetic nephropathy, reduces the area for filtration and leads eventually to sclerosis and renal failure (1, 2). However, the expansion of the mesangial extracellular matrix (ECM) 1 and the sclerosis that characterize diabetic nephropathy are preceded by a phenotypic activation and transient proliferation of the glomerular mesangial cells. This is followed by a prominent glomerular infiltration of monocytes and macrophages (3-5) that seems to play a key role in the subsequent mesangial matrix expansion, hypercellularity, and onset of proteinuria (6, 7). Nevertheless, the molecular mechanisms underlying glomerular infiltration by monocytes and macrophages are still unclear.The interaction of monocytes with mesangial cells in culture has been studied previously using U937 cells, a monocytic leukemic cell line that is a widely accepted model for monocyte adhesion (7,8), and mesangial cell cultures incubated in media with high glucose concentrations bind more U937 cells (7). Generally, the interactions between monocytes and resident cells involve: (i) monocyte cell surface proteins, including C...

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“…High glucose concentrations result in increased hyaluronan production in mesangial cells (38), renal proximal tubular cells (39), renal interstitial fibroblasts (40), and vascular smooth muscle cells (41,42). Hyaluronan cumulates in the glomeruli of diabetic animals (43), and hyperglycemia induces mesangial cells to synthesize a hyaluronan coat that can recruit inflammatory cells (44,45).…”

Section: Journal Of Biological Chemistry 5979mentioning

confidence: 99%

Hyaluronan Synthase 1 (HAS1) Requires Higher Cellular UDP-GlcNAc Concentration than HAS2 and HAS3*

Rilla

Oikari

Jokela

et al. 2013

Journal of Biological Chemistry

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Production of hyaluronan and chondroitin sulphate proteoglycans from human arterial smooth muscle--the effect of glucose, insulin, IGF-I or growth hormone

Cited by 39 publications

References 34 publications

Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

Hyaluronan Structures Synthesized by Rat Mesangial Cells in Response to Hyperglycemia Induce Monocyte Adhesion

Hyaluronan Synthase 1 (HAS1) Requires Higher Cellular UDP-GlcNAc Concentration than HAS2 and HAS3*

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