Low adipocyte IRS-1 protein expression is associated with an increased arterial stiffness in non-diabetic males

Sandqvist, Madeléne; Nyberg, G.; Hammarstedt, Ann; Klintland, Natalia; Gogg, Silvia; Caidahl, Kenneth; Åhrén, Bo; Smith, Ulf; Jansson, Per‐Anders

doi:10.1016/j.atherosclerosis.2004.11.006

Cited by 9 publications

(6 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Circulating levels of adiponectin were also significantly reduced. In a recent study, we were also able to show that low adipocyte IRS‐1 expression may be a marker not only for insulin resistance but also for arterial stiffness [49]. The data implicate that shared stressors, such as hyperglycemia and dyslipidaemia, cause oxidative stress and down‐regulation of IRS‐1 in fat cells and endothelial cells leading to insulin resistance and endothelial dysfunction.…”

Section: Insulin Resistance Mechanisms In Endothelial Cellsmentioning

confidence: 78%

Endothelial dysfunction in insulin resistance and type 2 diabetes

Jansson

2007

Journal of Internal Medicine

149

118

View full text Add to dashboard Cite

Abstract. Jansson P-A (Sahlgrenska University Hospital, Sahlgrenska, Göteborg, Sweden). Endothelial dysfunction in insulin resistance and type 2 diabetes (Review). J Intern Med 2007; 262: 173-183.Macrovascular disease is the number one killer in type 2 diabetes patients. The cluster of risk factors in the insulin resistance syndrome (IRS) partly explains this notion. Insulin action in muscle, liver or adipose tissue has been thoroughly described in the literature, whilst this has been less described for the endothelium. Insulin stimulates nitric oxide (NO) production in the endothelium and reduced bioavailability of NO is usually defined as endothelial dysfunction. This impairment might be related to defective insulin signalling in the endothelial cell. Therefore, insulin resistance mechanisms in the endothelial cell will be emphasized in this review. Imbalance between the vasodilating agent NO and the vasoconstrictor endothelin-1 (ET-1) contributes to endothelial dysfunction. Different methods and circulating markers to assess endothelial function will be outlined. Circulating markers of an activated endothelium appear long before type 2 diabetes develops suggesting a unique role of the endothelium in the pathophysiology of the disease. Hampered blood flow in nutritive capillaries due to endothelial dysfunction is coupled with decreased glucose uptake and hyperglycemia. The forearm model combined with muscle microdialysis enables us to measure interstitial glucose and an index for capillary recruitment, the permeability surface area (PS). Available data from this method suggest that capillary recruitment in response of insulin is impaired in insulin resistant human subjects.

show abstract

Section: Insulin Resistance Mechanisms In Endothelial Cellsmentioning

confidence: 78%

Endothelial dysfunction in insulin resistance and type 2 diabetes

Jansson

2007

Journal of Internal Medicine

149

118

View full text Add to dashboard Cite

show abstract

“…13,14 It is therefore interesting to note that fat cells from subjects with arterial stiffness display reduced intracellular amounts of the key insulin signalling protein Insulin Receptor Substrate-1. 32 Furthermore, adipose inflammation is an important factor contributing to insulin resistance and other metabolic complications. 33 Interestingly, adipocyte size correlates closely with the expression and secretion of the pro-inflammatory cytokine Tumour Necrosis Factor-alpha in lean healthy women 34 and with insulin resistance/dyslipidaemia in morbidly obese women.…”

Section: Discussionmentioning

confidence: 99%

Regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects

et al. 2014

View full text Add to dashboard Cite

show abstract

“…We have previously shown that IRS-1 protein expression, like GLUT4, is reduced in the adipose cells in insulin resistance and is, indeed, a biomarker of the IRS (12). Moreover, a group of subjects exhibiting low adipocyte IRS-1 expression displayed early signs of atherosclerosis, including an increased intima-media thickness (13) and an increased vascular stiffness as measured with pulse tonometry (24) compared with subjects with “normal” adipocyte IRS-1 expression. Animal studies have also shown that in the vasculature of obese Zucker rats, insulin resistance affects the PI3Kinase pathway but not other pathways of insulin signaling including the MAPK pathway (25).…”

Section: Discussionmentioning

confidence: 99%

Increased MAPK Activation and Impaired Insulin Signaling in Subcutaneous Microvascular Endothelial Cells in Type 2 Diabetes: The Role of Endothelin-1

2009

Self Cite

View full text Add to dashboard Cite

OBJECTIVETo establish a method for isolation and culture of subcutaneous microvascular endothelial cells (MVEC) from small human tissue biopsies to compare gene and protein expression of insulin signaling molecules in MVEC from insulin-resistant and healthy control subjects.RESEARCH DESIGN AND METHODSStromavascular cells from subcutaneous needle biopsies of type 2 diabetic and control subjects were expanded in culture and the endothelial cells selected with magnetic immune separation. Western blots and RT-PCR were used for protein and gene expression assays.RESULTSAt least 99% of the expanded primary MVEC could be characterized as endothelial cells. The expression of insulin receptors was low, but insulin increased tyrosine phosphorylation of both the insulin receptor and insulin receptor substrate (IRS)-1 and activated protein kinase B (PKB). The IRS-1 protein expression was reduced and the serine phosphorylation of PKB in response to insulin attenuated whereas basal and insulin-stimulated phosphorylation of extracellular signal–related kinase (ERK)1/2 was increased in type 2 diabetes MVEC. Endothelin (ET)-1 mRNA levels were significantly higher in type 2 diabetes cells. The addition of ET-1 increased the phosphorylation of mitogen-activated protein kinase (MAPK), an effect antagonized by the MEK-1 inhibitor PD98059. Furthermore, the endothelin ETA and ETB receptor antagonists BQ123 and BQ788 decreased basal MAPK activity in type 2 diabetes MVEC and prevented the ET-1–induced activation.CONCLUSIONSWe developed a system for isolation and culture of human MVEC from small needle biopsies. Our observations support the concept of “selective” insulin resistance, involving IRS-1 and the PI3kinase pathway, as an underlying factor for a dysregulated microvascular endothelium in type 2 diabetes. Our data also support a role of ET-1 for the increased MAPK activity seen in nonstimulated type 2 diabetes MVEC.

show abstract

Low adipocyte IRS-1 protein expression is associated with an increased arterial stiffness in non-diabetic males

Cited by 9 publications

References 34 publications

Endothelial dysfunction in insulin resistance and type 2 diabetes

Endothelial dysfunction in insulin resistance and type 2 diabetes

Regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects

Increased MAPK Activation and Impaired Insulin Signaling in Subcutaneous Microvascular Endothelial Cells in Type 2 Diabetes: The Role of Endothelin-1

Contact Info

Product

Resources

About