help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, N.-G.
Right arrow Articles by Reaven, G. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, N.-G.
Right arrow Articles by Reaven, G. M.
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 10 3485-3489
Copyright © 1999 by The Endocrine Society

From the Clinical Research Centers

Relationship Between Insulin Resistance, Soluble Adhesion Molecules, and Mononuclear Cell Binding in Healthy Volunteers1

Neng-Guin Chen, Margot Holmes and Gerald M. Reaven

Department of Medicine, Stanford University School of Medicine, Stanford, California 94305

Address correspondence and requests for reprints to: Gerald M. Reaven, M.D., Shaman Pharmaceuticals, Inc., 213 East Grand Avenue, South San Francisco, California 94080-4812. E-mail: greaven{at}shaman.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The relationship between insulin resistance, soluble adhesion molecules E-selectin (sE-selectin), intracellular adhesion molecule-1 (sICAM-1), and vascular adhesion molecule-1 (sVCAM-1), mononuclear cell binding to cultured endothelium, and lipoprotein concentrations were evaluated in 28 healthy, nondiabetic, and normotensive individuals. The mean (±SEM) lipid and lipoprotein concentrations were within the normal rage: cholesterol (199 ± 18 mg/dL); triglyceride (128 ± 12 mg/dL); low-density cholesterol (127 ± 8 mg/dL; and high-density cholesterol (47 ± 3 mg/dL). The results indicated that degree of insulin resistance was significantly correlated with concentrations of sE-selectin (r = 0.54, P < 0.005), sICAM-1 (r = 0.67, P < 0.001), and sVCAM-1 (r = 0.41, P < 0.05). Furthermore, the relationship between insulin resistance and both sE-selectin and sICAM-1 remained statistically significant when adjusted for differences in age, gender, body mass index, and all measures of lipoprotein concentrations. Finally, mononuclear cell binding correlated significantly with concentrations of sE-selectin (r = 0.54, P < 0.005) and sICAM-1 (r = 0.47, P < 0.01). These findings raise the possibility that previously described relationships between soluble adhesion molecules in patients with hypertension, type 2 diabetes, and dyslipidemia may be due to the presence of insulin resistance in these clinical syndromes and suggests that insulin resistance may predispose individuals to coronary heart disease by activation of cellular adhesion molecules.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
WE have recently presented preliminary evidence (1) that mononuclear cells isolated from insulin-resistant, nondiabetic subjects bound with enhanced avidity to cultured endothelium, and this was true of both normotensive and hypertensive subjects. Given the apparent importance of the interaction between circulating mononuclear cells and endothelium in the process of atherogenesis (2), understanding why the adherence to endothelium is increased in mononuclear cells isolated from insulin-resistant individuals is of great interest. Indeed it is possible that this phenomenon may help explain why insulin resistance and/or compensatory hyperinsulinemia increase risk of coronary heart disease (3, 4).

Although complete understanding of the mechanisms responsible for the increased adherence of mononuclear cells is lacking, this process seems to be modulated by various cell adhesion molecules (CAMs) (5, 6) including intracellular CAM-1 (ICAM-1), vascular CAM-1 (VCAM-1), and E-selectin. Soluble forms of these molecules are also in the circulation, and there are several studies (7, 8, 9, 10, 11, 12) demonstrating that soluble forms of CAMs are elevated in a variety of clinical conditions associated with increased risk of coronary heart disease (CHD), as well as insulin resistance (3, 4). Based on these relationships, we initiated the present study to test the hypothesis that the concentration of soluble CAMs would increase in insulin-resistant individuals, independently of the concomitant presence of hypertension, diabetes, or dyslipidemia.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The study population consisted of 28 healthy, nondiabetic volunteers. All individuals enrolled in the study were defined as healthy on the basis of medical history, physical examination, and normal results from routine laboratory tests and electrocardiography. In addition, they were nondiabetic by oral glucose tolerance test criteria (13). Volunteers were recruited on the basis of newspaper advertisements indicating our interest in the association between insulin resistance and CHD. The study protocol was approved by the Stanford University Institutional Review Board, and written, informed consent was obtained from all subjects.

All studies were performed at the General Clinical Research Center of Stanford University Medical Center. The degree of obesity was estimated by body mass index (BMI). Venous blood was obtained after an overnight fast for measurement of plasma glucose, insulin, cholesterol, triglyceride, and high-density (HDL) cholesterol concentrations, as described previously (14). In addition, plasma concentrations of soluble (s) VCAM-1 and ICAM-1 were determined using enzyme-linked immunoassay (ELISA) (kit no. 2170, sVCAM01, and kit no. 2169, sICAM-1; Immunotech, Marseille, France). Soluble E-selectin was determined using enzyme-linked immunoassay (Parameter, no. BBE 2B; R&D Systems, UK). The coefficient of variation was 4.8%, 6.9%, and 3.6%, respectively, for measurements of sICAM-1, sVCAM-1, and sE-selectin.

The ability of insulin to promote glucose uptake was estimated by a modification of the insulin suppression test as validated by our laboratory (15, 16). After an overnight fast, an intravenous catheter was placed in each of the volunteer’s arms. Blood was sampled from one arm for measurement of plasma glucose and insulin concentrations, and the contralateral arm was used for administration of test substances. Somatostatin was administered [250 µg/h in a solution containing 2.5% (wt/vol) human serum albumin] to suppress endogenous insulin secretion. Simultaneously, insulin and glucose were infused at rates of 25 mU/m2·min and 240 mg/m2·min, respectively. Blood was sampled every 30 min until 150 min had elapsed and then every 10 min until 180 min had elapsed. The four values obtained at 150, 160, 170, and 180 min were averaged and considered to represent the steady-state plasma glucose (SSPG) and insulin (SSPI) concentrations achieved during the infusion. Because SSPI concentrations are similar in all individuals, SSPG concentrations provide a direct estimate of insulin-mediated glucose disposal in each individual: the lower the SSPG, the more insulin sensitive the individual. The coefficient of variation of the four measurements used to determine SSPG and SSPI was 5.6% and 6.1%, respectively. Two-way analysis of variance, time point, and patient indicated that the possibility that a nonsteady state existed in either measurement could be rejected (P = 0.9).

In addition, venous blood drawn after an overnight fast was used for isolation of mononuclear cells for adhesion studies (14). The viability of the isolated cells was assessed by trypan blue exclusion, and mononuclear cells isolated in this manner contain ~3–10% monocytes, ~45% T-lymphocytes, and ~45% B-lymphocytes. Binding assays with the isolated mononuclear cells were performed with ECV 304 cells, a human umbilical vein endothelial cell-derived transformed cell line. Endothelial cells were maintained in M199 with 10% fetal calf serum, split into 35-mm diameter wells on 6-well plates 3 days before adhesion assays, and confluency was confirmed before binding studies. Adhesion of mononuclear cells to endothelial cells was assessed using previously established methods (14). Briefly, freshly isolated human mononuclear cell suspensions (3 x 106/mL final concentration) were added to the wells containing confluent endothelial monolayers, the 6-well plates were transferred to a rocking platform, where they were rocked for 30 min at room temperature, turning the 6-well plates 90 degrees at 15 min. After 30 min, nonadherent cells were removed, and plates rocked for an additional 5 min with fresh binding buffer. Binding buffer was then replaced with Hank’s balanced salt solution containing 2% glutaraldehyde to fix the remaining cells. Adherent cells were quantified by videomicroscopy using a computer-aided image analysis system (Image Analyst; Automatix Corp., Boston, MA).

Data are expressed as a mean (±SEM). Simple Pearson product-moment correlation coefficients were calculated to determine relations between variables of interest. Partial correlation coefficients were calculated to determine correlations between two variables of interest when adjusted for the concomitant effects of age, gender, BMI, fasting insulin, triglyceride, and low-density lipoprotein (LDL) and HDL cholesterol concentrations. Multiple regression analysis was performed with the dependent variable being mononuclear cell binding. Finally, Student’s nonpaired t test was used to compare an insulin-resistant group to an insulin-sensitive group.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The clinical and metabolic characteristics of the experimental population are listed in Table 1Go. It can be seen that considerable variability existed for all of the experimental variables, with the mean values for all the measurements being within the normal range.


View this table:
[in this window]
[in a new window]
  		Table 1. Clinical and metabolic characteristics of the experimental population

 
Fig. 1Go illustrates the relationship between SSPG and sE-selectin, sICAM-1, and sVCAM-1. It can be seen that SSPG correlated to all three soluble adhesion molecules with varying degrees of significance: sE-selectin (r = 0.54, P < 0.005), sICAM-1 (r = 0.67, P < 0.001), and sVCAM-1 (r = 0.41, P < 0.05). SSPG concentrations remained significantly correlated with both sE-selectin (r = 0.62, P < 0.05) and sICAM-1 (r = 0.58, P < 0.01) when corrected for differences in all other variables.



View larger version (15K):
[in this window]
[in a new window]
  		Figure 1. Relationship between insulin resistance (SSPG) and circulating soluble adhesion molecules E-selectin (top), ICAM-1 (middle), and VCAM-1 (bottom).

 
In an effort to further evaluate the effect of resistance to insulin-mediated glucose disposal on concentrations of soluble adhesion molecules, the 26 volunteers were divided into two groups of 13 each, using a SSPG concentration of 150 mg/dL as the cut-point. The two groups thus formed were similar in terms of age (58 ± 4 vs. 60 ± 3 yr) and BMI (26.7 ± 3.1 vs. 28.0 ± 2.7 kg/m2), but were significantly (P < 0.001) different in terms of SSPG concentration (92 ± 10 vs 233 ± 12 mg/dl). The group with the highest SSPG concentrations (the insulin-resistant group) also had significantly (P < 0.005) higher concentrations (ng/mL) of sE-selectin (42 ± 3 vs. 29 ± 2), sICAM (528 ± 32 vs. 412 ± 19), and sVCAM-1 (1097 ± 101 vs. 766 ± 58). In addition, mononuclear cell binding was also greater in the insulin-resistant group (35 ± 2 vs. 24 ± 3 cells per high-power field, P < 0.001).

The relationship between the three soluble adhesion molecules and mononuclear cell binding is depicted in Fig. 2Go. Both sE-selectin (r = 0.54, P < 0.005) and sICAM-1 (r = 0.47, P < 0.01) were also related to the adherence of mononuclear cells to endothelium, but concentrations of sVCAM-1 were not significantly correlated (r = 0.20, P = 0.30).



View larger version (15K):
[in this window]
[in a new window]
  		Figure 2. Relationship between circulating soluble adhesion molecules E-selectin (top), ICAM-1 (middle), and VCAM-1 (bottom) and adherence of isolated mononuclear cells to cultured endothelial cells.

 
To gain insight into the independence of these various relationships, multiple regression analysis was performed. The first model evaluated contained mononuclear cell binding as the dependent variable, with age, gender, BMI, lipoprotein concentrations, SSPG, and the three soluble adhesion molecules serving as the independent variables (Table 2Go). When this was done, only SSPG was significantly correlated (P = 0.005). However, because SSPG and the adhesion molecules themselves were highly significantly correlated, we removed SSPG from the model described above (Table 3Go). The results of this analysis indicated that sE-selectin (P = 0.04), sICAM-1 (P = 0.05), and plasma triglyceride concentration (P = 0.04) were significantly related to mononuclear cell binding when insulin resistance was no longer entered into the model.


View this table:
[in this window]
[in a new window]
  		Table 2. Multiple regression analysis of the relationship between mononuclear cell binding and other related variables1

 

View this table:
[in this window]
[in a new window]
  		Table 3. Multiple regression analysis of the relationship between mononuclear cell binding and relevant variable—excluding SSPG1

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Several previous publications have shown that soluble adhesion molecules are increased in patients with hypertriglyceridemia, essential hypertension, gestational diabetes, or type 2 diabetes (7, 8, 9, 10, 11, 12, 17). The common element in these disparate clinical syndromes is the presence of resistance to insulin-mediated glucose disposal, raising the possibility that the increase in circulating soluble adhesion molecules is secondary to insulin resistance. The current study was initiated to test this hypothesis, and the results presented certainly provide support for this point of view. Specifically, SSPG (the estimate of insulin resistance) was significantly correlated with sE-selectin (r = 0.54, P < 0.005), sICAM-1 (r = 0.67, P < 0.001), and sVCAM-1 (r = 0.41, P < 0.05). Furthermore, the correlation coefficients between SSPG and sE-selectin (r = 0.62, P < 0.05) and sICAM-1 (r = 0.58, P < 0.01) remained highly significant when corrected for differences in age, gender, BMI, and plasma concentrations of triglyceride, LDL cholesterol, and HDL cholesterol. Finally, the 13 most insulin-resistant individuals had significantly higher (P < 0.005) concentrations of all three soluble adhesion molecules as compared with the insulin-sensitive volunteers.

In addition to the relationship between insulin resistance and soluble adhesion molecules, the current results have also defined associations between enhanced mononuclear cell binding to endothelium and sE-selectin and sICAM-1. Indeed, concentrations of both sE-selectin and sICAM-1 and increased mononuclear cell binding were associated to a significant degree.

The presence of correlations between variables neither proves causality nor defines the manner in which they are related. On the other hand, they can provide the foundation necessary to offer certain hypotheses. At the simplest level, the results presented support the view that insulin resistance may account for the increases in soluble adhesion molecules in patients with gestational diabetes, type 2 diabetes, dyslipidemia, and hypertension described in previous studies (7, 8, 9, 10, 11, 12, 17). Furthermore, they provide the ingredients that may help explain why CHD is enhanced in syndromes characterized by insulin resistance. We have recently shown in a prospective study that insulin resistance predicted the development of CHD (18), and increases in sICAM-1 concentrations have also been shown to predict future myocardial infarction in apparently healthy men (19). Based on these findings, it could be postulated that insulin resistance increases the expression of E-selectin and ICAM-1 on endothelium, leading to the enhanced release of the soluble forms of these CAMs into the circulation. This latter step is supported by in vitro studies showing that the amount of sE-selectin and sICAM-1 released from activated endothelial cells was directly correlated with the degree of cell surface expression (20). This formulation provides an explanation for the statistically significant relationship between insulin resistance and the soluble adhesion molecules. In addition to accounting for the increase in sE-selectin and sICAM-1, interaction between circulating mononuclear cells and the enhanced expression of CAMs could bring about their greater adherence to endothelium.

The sequence of events postulated above is not the only interpretation of our results. For example, increases in CAMs in insulin-resistant individuals could be secondary to subclinical cardiovascular disease, a possibility consistent with evidence that concentrations of sE-selectin and sICAM-1 are correlated with degree of carotid artery atherosclerosis (11). Indeed, there is no reason to suggest that this possibility is less attractive than the notion that the activity of CAMs is increased in insulin-resistant subjects.

In conclusion, the concentration of soluble adhesion molecules E-selectin, ICAM-1, and VCAM-1 are increased in proportion to the degree of insulin resistance in healthy normotensive, nondiabetic volunteers, independent of the presence of diabetes, hypertension, or apparent CHD. In addition, enhanced mononuclear cell binding was associated with increases in sE-selectin and sICAM-1. These results provide a possible explanation for why insulin-resistant individuals are at risk to develop CHD (3, 4, 18).


   Footnotes
 
1 Supported by Research Grants RR-00070 and HL-08506 and Training Grant HL-07708 from the NIH. Back

Received April 29, 1999.

Revised June 28, 1999.

Accepted July 6, 1999.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Chen N-G, Abbasi F, Chen Y-DI, Cooke JP, Tsao PS, Reaven GM. 1998 Adherence of mononuclear cells to endothelium is increased in patients with hypertension. J Invest Med. 46:108A.
  2. Ross R. 1986 The pathogenesis of atherosclerosis. N Engl J Med. 314:488–500.[Medline]
  3. Reaven GM. 1988 Role of insulin resistance in human disease. Diabetes. 37:1595–1607.[Abstract]
  4. Chen Y-DI, Reaven GM. 1997 Insulin resistance and atherosclerosis. Diabetes Rev. 5:331–342.
  5. Springer TA. 1990 Adhesion receptors of the immune system. Nature. 346:425–434.[CrossRef][Medline]
  6. Carlos TM, Harlan JM. 1994 Leukocyte-endothelial adhesion molecules. Blood. 84:2068–2101.[Abstract/Free Full Text]
  7. Cominacini L, Fratta Pasini A, Garbin U, et al.1995 Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control. Diabetologia. 38:1122–1124.
  8. Lip GYH, Blann AD, Zarifis J, Beevers M, Lip PL, Beevers DG. 1995 Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension: implications for atherogenesis? A preliminary report. J Hypertens. 13:1674–1678.[Medline]
  9. Ceriello A, Falleti E, Bortolotti N, et al. 1996 Increased circulating intercellular adhesion molecule-1 levels in type II diabetic patients: the possible role of metabolic control and oxidative stress. Metabolism. 45:498–500.[CrossRef][Medline]
  10. Desouza CA, Dengel DR, Macko RF, Cox K, Seals DR. 1997 Elevated levels of circulating cell adhesion molecules in uncomplicated essential hypertension. Am J Hypertens. 10:1335–1341.[Medline]
  11. Abe Y, El-Masri B, Kimball KT, et al. 1998 Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion. Arterioscler Thromb Vasc Biol. 18:723–731.[Abstract/Free Full Text]
  12. Ferri C, Desideri G, Baldoncini R, et al. 1998 Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. Diabetes. 47:660–667.[Abstract]
  13. National Diabetes Data Group. 1979 Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes. 28:1039–1057.[Medline]
  14. Carantoni M, Abbasi F, Chu L, et al. 1997 Adherence of mononuclear cells to endothelium in vitro is increased in patients with NIDDM. Diabetes Care. 20:1462–1465.[Abstract]
  15. Harano Y, Ohgaku S, Hidaka H, et al. 1977 Glucose, insulin and somatostatin infusion for the determination of insulin sensitivity. J Clin Endocrinol Metab. 45:1124–1127.[Abstract/Free Full Text]
  16. Greenfield MS, Doberne L, Kraemer FB, Tobey TA, Reaven GM. 1981 Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes. 30:387–392.[Abstract]
  17. Kautzky-Willer A, Fasching B, Jilma B, Waldhausl W, Wagner OF. 1997 Persistent elevation and metabolic dependence of circulating E-selectin after delivery in women with gestational diabetes mellitus. J Clin Endocrinol Metab. 82:4117–4121.[Abstract/Free Full Text]
  18. Yip J, Facchini FS, Reaven GM. 1998 Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab. 83:2773–2776.[Abstract/Free Full Text]
  19. Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J. 1998 Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 351:88–92.[CrossRef][Medline]
  20. Leeuwenberg JFM, Neefjes EF, Smeets JJ, et al. 1992 E-selectin and intercellular adhesion molecule-1 are released by activated human endothelial cells in vitro. Immunology. 77:543–549.[Medline]



This article has been cited by other articles:


Home page
 EndocrinologyHome page
G. Li, E. J. Barrett, S.-H. Ko, W. Cao, and Z. Liu
Insulin and Insulin-Like Growth Factor-I Receptors Differentially Mediate Insulin-Stimulated Adhesion Molecule Production by Endothelial Cells
Endocrinology, August 1, 2009; 150(8): 3475 - 3482.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. M. Whetzel, D. T. Bolick, and C. C. Hedrick
Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3
Am J Physiol Cell Physiol, February 1, 2009; 296(2): C339 - C345.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
S. Lee, N. Gungor, F. Bacha, and S. Arslanian
Insulin Resistance: Link to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth
Diabetes Care, August 1, 2007; 30(8): 2091 - 2097.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Y. Song, J. E. Manson, L. Tinker, N. Rifai, N. R. Cook, F. B. Hu, G. S. Hotamisligil, P. M. Ridker, B. L. Rodriguez, K. L. Margolis, et al.
Circulating Levels of Endothelial Adhesion Molecules and Risk of Diabetes in an Ethnically Diverse Cohort of Women
Diabetes, July 1, 2007; 56(7): 1898 - 1904.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
S. Kapiotis, G. Holzer, G. Schaller, M. Haumer, H. Widhalm, D. Weghuber, B. Jilma, G. Roggla, M. Wolzt, K. Widhalm, et al.
A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes
Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2541 - 2546.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
T. McLaughlin, S. Carter, C. Lamendola, F. Abbasi, G. Yee, P. Schaaf, M. Basina, and G. Reaven
Effects of moderate variations in macronutrient composition on weight loss and reduction in cardiovascular disease risk in obese, insulin-resistant adults.
Am. J. Clinical Nutrition, October 1, 2006; 84(4): 813 - 821.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
W.-Y. Zhang, E. Schwartz, Y. Wang, J. Attrep, Z. Li, and P. Reaven
Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells
Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 514 - 519.
[Abstract] [Full Text] [PDF]

Home page
 Vasc MedHome page
K. Sydow, C. E Mondon, and J. P Cooke
Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA
Vascular Medicine, July 1, 2005; 10(1_suppl): S35 - S43.
[Abstract] [PDF]

Home page
 Vasc MedHome page
K. Sydow, C. E Mondon, and J. P Cooke
Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA
Vascular Medicine, May 1, 2005; 10(2_suppl): S35 - S43.
[Abstract] [PDF]

Home page
 Diabetes and Vascular Disease ResearchHome page
J. W Chu, F. Abbasi, C. Lamendola, T. McLaughlin, G. M Reaven, and P. S Tsao
Effect of rosiglitazone treatment on circulating vascular and inflammatory markers in insulin-resistant subjects
Diabetes and Vascular Disease Research, February 1, 2005; 2(1): 37 - 41.
[Abstract] [PDF]

Home page
 ANGIOLOGYHome page
J. Okapcova and D. Gabor
The Levels of Soluble Adhesion Molecules in Diabetic and Nondiabetic Patients with Combined Hyperlipoproteinemia and the Effect of Ciprofibrate Therapy
Angiology, November 1, 2004; 55(6): 629 - 639.
[Abstract] [PDF]

Home page
 ANGIOLOGYHome page
J. Okapcova and D. Gabor
The Levels of Soluble Adhesion Molecules in Diabetic and Nondiabetic Patients with Combined Hyperlipoproteinemia and the Effect of Ciprofibrate Therapy
Angiology, November 1, 2004; 55(6): 629 - 639.
[Abstract] [PDF]

Home page
 Clin. Chem.Home page
C. Schmid, P. Wiesli, R. Bernays, K. Bloch, J. Zapf, C. Zwimpfer, C. Ghirlanda, and M. Brandle
Decrease in sE-Selectin after Pituitary Surgery in Patients with Acromegaly
Clin. Chem., March 1, 2004; 50(3): 650 - 652.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
G. Reaven and P. S. Tsao
Insulin resistance and compensatory hyperinsulinemia: The key player between cigarette smoking and cardiovascular disease?
J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1044 - 1047.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
T. Abiko, A. Abiko, A. C. Clermont, B. Shoelson, N. Horio, J. Takahashi, A. P. Adamis, G. L. King, and S.-E. Bursell
Characterization of Retinal Leukostasis and Hemodynamics in Insulin Resistance and Diabetes: Role of Oxidants and Protein Kinase-C Activation
Diabetes, March 1, 2003; 52(3): 829 - 837.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
M. C. Stuhlinger, F. Abbasi, J. W. Chu, C. Lamendola, T. L. McLaughlin, J. P. Cooke, G. M. Reaven, and P. S. Tsao
Relationship Between Insulin Resistance and an Endogenous Nitric Oxide Synthase Inhibitor
JAMA, March 20, 2002; 287(11): 1420 - 1426.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
K. Matsumoto, Y. Sera, Y. Abe, Y. Ueki, and S. Miyake
Serum Concentrations of Soluble Vascular Cell Adhesion Molecule-1 and E-Selectin Are Elevated in Insulin-Resistant Patients With Type 2 Diabetes
Diabetes Care, September 1, 2001; 24(9): 1697 - 1698.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. D. Blann and G. Y. H. Lip
Editorial: Cell Adhesion Molecules in Cardiovascular Disease and Its Risk Factors--What Can Soluble Levels Tell Us?
J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1745 - 1747.
[Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
B. Jilma, S. Dallinger, N. Hergovich, H.-G. Eichler, V. Richter, and O. F. Wagner
Effects of Hyperinsulinemia on Plasma Levels of Circulating Adhesion Molecules
J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1748 - 1751.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M. Montagnani, I. Golovchenko, I. Kim, G. Y. Koh, M. L. Goalstone, A. N. Mundhekar, M. Johansen, D. F. Kucik, M. J. Quon, and B. Draznin
Inhibition of Phosphatidylinositol 3-Kinase Enhances Mitogenic Actions of Insulin in Endothelial Cells
J. Biol. Chem., January 11, 2002; 277(3): 1794 - 1799.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, N.-G.
Right arrow Articles by Reaven, G. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, N.-G.
Right arrow Articles by Reaven, G. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals