Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Pathophysiology/Complications

Plasma Resistin, Associated With Single Nucleotide Polymorphism −420, Is Correlated With Insulin Resistance, Lower HDL Cholesterol, and High-Sensitivity C-Reactive Protein in the Japanese General Population

  1. Haruhiko Osawa, MD, PHD1,
  2. Yasuharu Tabara, PHD2,
  3. Ryuichi Kawamoto, MD, PHD3,
  4. Jun Ohashi, PHD4,
  5. Masaaki Ochi, BS1,
  6. Hiroshi Onuma, MD, PHD1,
  7. Wataru Nishida, MD, PHD1,
  8. Kazuya Yamada, PHD56,
  9. Jun Nakura, MD, PHD7,
  10. Katsuhiko Kohara, MD, PHD7,
  11. Tetsuro Miki, MD, PHD7 and
  12. Hideichi Makino, MD, PHD1
  1. 1Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
  2. 2Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Ehime, Japan
  3. 3Department of Internal Medicine, Seiyo-city Nomura Hospital, Ehime, Japan
  4. 4Department of Human Genetics, School of International Health, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
  5. 5Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
  6. 6CREST, Japan Science and Technology Agency, Fukui, Japan
  7. 7Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
  1. Address correspondence and reprint requests to H. Osawa, MD, PhD, Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. E-mail: harosawa{at}m.ehime-u.ac.jp. Or H. Makino, MD, PhD, Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. E-mail: hidemak{at}m.ehime-u.ac.jp
Diabetes Care 2007 Jun; 30(6): 1501-1506. https://doi.org/10.2337/dc06-1936
PreviousNext
  • Article
  • Figures & Tables
  • Info & Metrics
  • PDF
Loading

Abstract

OBJECTIVE—Resistin, secreted from adipocytes, causes insulin resistance in rodents. We previously reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at −420 increases type 2 diabetes susceptibility by enhancing promoter activity. We report here on the relation between plasma resistin and either SNP −420 genotype or factors related to insulin resistance.

RESEARCH DESIGN AND METHODS—We cross-sectionally analyzed 2,078 community-dwelling Japanese subjects attending a yearly medical checkup. The SNP −420 genotype was determined by TaqMan analysis. Fasting plasma resistin was measured using an enzyme-linked immunosorbent assay kit.

RESULTS—Plasma resistin was associated with the SNP −420 genotype (P < 0.0001), which was highest in G/G followed by C/G and C/C. Plasma resistin was higher in elderly individuals, female subjects, nondrinkers, and subjects with high blood pressure (P < 0.001, 0.003, <0.001, and 0.001, respectively). Simple regression analysis revealed that age, female sex, homeostasis model assessment of insulin resistance (HOMA-IR) index, systolic blood pressure, low HDL cholesterol, and high-sensitivity C-reactive protein (hs-CRP) were positively correlated with plasma resistin (P < 0.001, 0.003, <0.001, 0.004, <0.001, and 0.003, respectively). Multiple regression analysis adjusted for age, sex, and BMI revealed that plasma resistin was an independent factor for HOMA-IR, low HDL cholesterol, and hs-CRP (P = 0.001, <0.001, and 0.006, respectively).

CONCLUSIONS—Plasma resistin was associated with SNP −420 and was correlated with insulin resistance, low serum HDL cholesterol, and high hs-CRP in the Japanese general population.

  • CRP, C-reactive protein
  • CVD, cardiovascular disease
  • FPG, fasting plasma glucose
  • HOMA-IR, homeostasis model assessment of insulin resistance
  • hs-CRP, high-sensitivity CRP
  • IRI, immunoreactive insulin
  • SNP, single nucleotide polymorphism
  • SBP, systolic blood pressure

Resistin, secreted from adipocytes of mice, antagonizes insulin action in vitro and in vivo (1,2). Serum resistin is increased in obese diabetic mice and is reduced by insulin sensitizers, peroxisome proliferator–activated receptor γ ligands (1,2). Overexpression of resistin gene in the liver increases serum resistin and insulin resistance (3), whereas its disruption reduces fasting plasma glucose (FPG) (4). Therefore, an elevation in serum resistin appears to cause insulin resistance in rodents, although some other studies are not in agreement with this conclusion (5).

Type 2 diabetes is characterized by insulin resistance in insulin target tissues (6). Major genetic factors of type 2 diabetes, a probable polygenic disease, remain to be identified, whereas it has been reported that some single nucleotide polymorphisms (SNPs) are associated with type 2 diabetes (7). We recently reported that the G/G genotype of a human resistin gene (RETN) SNP at −420 (rs1862513) was associated with type 2 diabetes susceptibility (8). Of the frequent SNPs in the linkage disequilibrium area including SNP −420, only SNP −420 was significantly associated with type 2 diabetes. In vitro, Sp1/3 transcription factors specifically recognized G at −420 and enhanced resistin promoter activity. Subjects with G/G genotype had the highest serum resistin, followed by C/G and C/C (8,9). Thus, the association between SNP −420 and serum resistin in the general population merits further investigation.

It remains controversial whether circulating resistin levels are associated with insulin resistance, type 2 diabetes, or adiposity in humans (9–17). It has been reported that resistin is increased in type 2 diabetes (9,13) and in obesity (10,12). McTernan et al. (15) and Youn et al. (17) reported that resistin is increased in type 2 diabetes but not associated with BMI, although the role of obesity was not the primary focus of the former's study. Silha et al. (16), but not Lee et al. (14), found an association between resistin and insulin resistance. No association was detected between resistin and either type 2 diabetes or obesity (14). The discrepancy among previous reports may be resolved by analyzing a larger number of samples.

Metabolic syndrome, a cluster of abnormalities including central obesity, glucose intolerance or diabetes, hypertension, and dyslipidemia (high triglyceride levels and/or low HDL cholesterol), increases the risk of cardiovascular disease (CVD) (18). Because underlying insulin resistance could be fundamental for this syndrome, the relation between resistin and metabolic syndrome factors should be assessed.

To determine the relation between plasma resistin and either SNP −420 or factors related to insulin resistance, we cross-sectionally analyzed 2,078 subjects. Plasma resistin was associated with SNP −420 and was correlated with homeostasis model assessment of insulin resistance (HOMA-IR), lower HDL cholesterol, and high-sensitivity C-reactive protein (hs-CRP).

RESEARCH DESIGN AND METHODS

All subjects were native to Japan. We analyzed community-dwelling subjects attending a yearly medical checkup in a rural town located in Ehime prefecture, Japan, in 2002. Of the 2,889 subjects who agreed to participate, 2,078, for whom overnight fasting plasma samples (>11 h) were available, were analyzed for plasma resistin levels. Because of the availability of plasma samples, immunoreactive insulin (IRI) and hs-CRP were measured in 2,017 and 1,875 subjects, respectively. Of the 2,078 subjects, 157 with A1C levels <5.6%, FPG levels <110 mg/dl, no history of diabetes, and no evidence of diabetes within first-degree relatives were used as nondiabetic control subjects in a previous study (9). There was no overlapping of samples between the present study and the other previous study (8). Of the 2,078 subjects, 151 were considered diabetic because they were being treated with antihyperglycemic agents or had FPG levels of ≥126 mg/dl. The association between SNP −420 and diabetes was not significant, possibly because of the lack of power using the small numbers of diabetic subjects. The plasma samples were immediately separated, frozen, and stored at −80°C. The baseline characteristics of the study subjects, such as alcohol habituation, history or symptoms of CVD, and medication, were investigated in an individual interview using a structured questionnaire. The clinical characteristics of these subjects are summarized in Table 1. All subjects were informed of the purpose of the study and their consent was obtained. The study was approved by the ethics committee of the Ehime University Graduate School of Medicine. Definitions used are as follows: obesity, BMI ≥25 kg/m2; impaired glucose tolerance, FPG ≥110 mg/dl (6.1 mmol/l) and/or under medication of antihyperglycemic agents; high blood pressure, systolic blood pressure (SBP) ≥140 mmHg and/or diastolic pressure ≥90 mmHg and/or under medication with antihypertensive agents; hypertriglyceridemia, triglyceride levels ≥150 mg/dl (1.69 mmol/l) and/or under medication with antihyperlipidemic agents; and low HDL cholesterol, HDL cholesterol <40 mg/dl (1.04 mmol/l). CVD includes stroke, myocardial infarction, and angina pectoris. Because Japanese individuals are generally leaner than Caucasians, BMI ≥25 kg/m2 was used as the standard cutoff value for the diagnosis of obesity (19). Waist circumference data were not available in this study. Blood pressure was measured using an automatic cuff-oscillometric device with an appropriately sized cuff on the left arm (BP-103i; Colin, Aichi, Japan) after a resting period of at least 5 min in the sitting position.

SNP typing

SNP −420 was typed by TaqMan analysis (Applied Biosystems). The probes used were VIC 5′-CATGAAGACGGAGGCC-3′ for −420C and FAM 5′-ATGAAGAGGGAGGCC-3′ for −420G. Forward and reverse primers were 5′-CCACCTCCTGACCAGTCTCT-3′ and 5′-AGCCTTCCCACTTCCAACAG-3′, respectively. When required, PCR direct sequencing was performed as previously described (8,20).

Measurement of plasma resistin and hs-CRP levels

Plasma resistin was measured using a human resistin enzyme-linked immunosorbent assay kit (LINCO Research) following the manufacturer's protocol as described (8). The linearity was maintained <0.16 ng/ml. Inter- and intra-assay coefficients of variation (CVs) were 6.9 and 1.7% (low levels) and 7.2 and 8.1% (high levels), respectively. The kit used had a good correlation with the other kit (r = 0.978; y = 2.216x + 8.0, where y is this kit and x is BioVender's kit). Plasma hs-CRP concentration was measured using a previously validated assay system (Dade Behring) (21). Inter- and intra-assay CVs were 3.2 and 6.7%, respectively.

Statistical analysis

To examine effects of SNP −420 on plasma resistin, a multiple regression analysis involving SNP −420, age, sex, and BMI as independent variables and plasma resistin as a dependent variable was used. In this analysis, the genotypes for SNP −420, C/C, C/G, and G/G were denoted by two dummy variables (c1 and c2 [0 and 0, 1 and 0, and 0 and 1, respectively]). To examine the relation of plasma resistin with age, sex, BMI, SBP, HDL cholesterol, triglyceride levels, FPG, IRI, HOMA-IR, or hs-CRP, simple regression analysis involving plasma resistin as a dependent variable was performed. A multiple regression analysis was then performed using only the significant factors. HOMA-IR, HDL cholesterol, hs-CRP, or SBP was analyzed as a dependent variable, and plasma resistin, age, sex, and BMI were involved as independent variables. CVD was involved as a dependent variable in logistic regression analysis. ANOVA was used where indicated. All analyses were performed with SPSS version 14.0J (SPSS, Chicago, IL). Bonferroni's correction was applied to the initial analyses of the relation between plasma resistin and either categories (raw P value ×9 for ANOVA) or continuous parameters (raw P value ×10 for simple regression analysis) and the subsequent multiple and logistic regression analyses using factors selected from these results (raw P value ×5). The proportion of variance of plasma resistin explained by SNP −420 was assessed based on results of a simple regression analysis. Power was calculated based on the observed effect and sample sizes using general linear model for ANOVA (simple and multiple regression analyses with α = 0.05). Null hypotheses were rejected at P < 0.05.

RESULTS

SNP −420 was associated with plasma resistin in the Japanese general population

We first assessed plasma resistin based on each genotype of SNP −420 in 2,078 subjects (Fig. 1A). Fasting plasma resistin was highest in subjects with the G/G genotype, followed in order by those with C/G and those with C/C (F = 368.6, P < 0.0001, power = 0.999). This association was consistent when analyzed in either male (F = 150.6, P < 0.0001) or female (F = 221.3, P < 0.0001) subjects. When 50, 20, and 5% of the subjects were randomly selected and compared using the SPSS program, these P values were consistently low (P < 0.0001). Therefore, plasma resistin was associated with SNP −420 in this population.

We then examined the number of subjects in each 2.5 ng/ml range of plasma resistin concentration based on the SNP −420 genotype (Fig. 1B). The plasma resistin at the highest number of subjects with each genotype appears to be in the order of G/G > C/G > C/C. The range of plasma resistin was broadest in subjects with G/G, followed in order by C/G and C/C (1.9–52.7, 2.2–46.2, and 2.2–35.2 ng/ml, respectively), suggesting that factors other than SNP −420 genotype may affect plasma resistin.

To examine isolated effects of SNP −420 on plasma resistin, a multiple regression analysis involving SNP −420, age, sex, and BMI as independent variables was used. The SNP −420 genotype including G alleles (G/G vs. C/C, P < 0.001, power = 0.999 and C/G vs. C/C, P < 0.001, power = 0.999), higher age (P < 0.001, power = 0.999), and female sex (P = 0.001, power = 0.894), but not higher BMI (P = 0.195, power = 0.254), was positively correlated with plasma resistin. The standardized coefficient (β) of the G/G genotype compared with C/C was highest (β = 0.480), followed by that of C/G compared with C/C (β = 0.384) (age, β = 0.100; female sex, β = 0.060; and BMI, β = 0.024). Therefore, SNP −420 genotype was the strongest determinant of plasma resistin among these factors. The contribution of this genotype to the observed total variance of resistin (R2) was 26.1%.

Plasma resistin was higher in elderly individuals, female subjects, nondrinkers, and subjects with high blood pressure

We then examined mean plasma resistin in each category without considering the SNP −420 genotype. Plasma resistin was higher in elderly individuals (aged ≥65 years) (mean ± SD 12.2 ± 7.1 vs. 10.9 ± 6.1; ANOVA P < 0.001, power = 0.994), female subjects (11.9 ± 6.6 vs. 11.0 ± 6.6; P = 0.003, power = 0.852), nonhabitual alcohol drinkers (12.0 ± 6.7 vs. 10.4 ± 6.3; P < 0.001, power = 0.999), subjects with high blood pressure (11.9 ± 6.9 vs. 11.0 ± 6.2; P = 0.001, power = 0.905), those with low HDL cholesterol (13.0 ± 8.3 vs. 11.4 ± 6.5; P = 0.014, power = 0.693), and those with a history of CVD (12.5 ± 6.7 vs. 11.4 ± 6.6; P = 0.045, power = 0.516). Age, sex, alcohol drinking, and high blood pressure remained significant after Bonferroni's correction. Obesity (P = 0.613, power = 0.080), IGT (P = 0.733, power = 0.063), or hypertriglyceridemia (P = 0.497, power = 0.104) was not associated with plasma resistin.

Age, female sex, SBP, low HDL cholesterol, HOMA-IR, and hs-CRP were correlated with plasma resistin

We then examined which factors are correlated with plasma resistin (Table 2). Simple regression analysis revealed that age, female sex, SBP, low HDL cholesterol, IRI, HOMA-IR, and hs-CRP were correlated with plasma resistin. Each of these P values remains significant after Bonferroni's correction. BMI, triglyceride levels, and FPG were not correlated with plasma resistin. Therefore, with possible effects of age and sex, high plasma resistin was correlated with insulin resistance, low HDL cholesterol, high SBP, and high hs-CRP.

Plasma resistin was correlated with HOMA-IR, low HDL cholesterol, or hs-CRP, independent of age, sex, and BMI

To examine isolated effects of plasma resistin on each factor, a multiple regression analysis adjusted for age, sex, and BMI was performed (Table 3). Factors significantly associated with plasma resistin in Table 2, namely, HOMA-IR, HDL cholesterol, hs-CRP, and SBP, were individually analyzed as a dependent variable. Among these factors, only HOMA-IR, low HDL cholesterol, and hs-CRP were correlated with plasma resistin, with the caution that plasma resistin has a relatively small effect on these parameters based on the regression coefficients. Therefore, plasma resistin, associated with SNP −420, was correlated with HOMA-IR, low HDL cholesterol, and hs-CRP, independent of age, sex, and BMI.

CONCLUSIONS

Our cross-sectional study that included 2,078 subjects from the Japanese general population shows that plasma resistin was associated with SNP −420. Plasma resistin was higher in the elderly, female subjects, nondrinkers, and subjects with high blood pressure. Multiple regression analysis adjusted for age, sex, and BMI revealed that plasma resistin was an independent factor for HOMA-IR, low HDL cholesterol, and hs-CRP.

We found that SNP −420 was associated with plasma resistin in the order G/G > C/G > C/C in a large number of samples. This finding provides strong evidence for a tight correlation between a functional promoter SNP and its gene product as the final output in humans. The association is also supported by studies in which smaller numbers of samples were used, namely by Cho et al. (11) and ourselves (8). Haplotypes including SNP −420 also show this similar tendency in Japanese subjects (22). A total of four independent groups reported that the activity of the mutant RETN promoter including −420G is higher than that of the wild type including −420C in vitro (8,11,22,23). Therefore, we propose that SNP −420 is a determinant of plasma resistin. Because only SNP −420 was typed in this study, the other SNPs in RETN should be analyzed to further examine this hypothesis.

Our findings have shown that plasma resistin was positively associated with HOMA-IR, independent of age, sex, and BMI. To our knowledge, the positive correlation between circulating resistin and HOMA-IR in humans is supported in 2 of >10 previous studies, whereas the role of resistin as a factor inducing insulin resistance has been established in mice (16,24). The lower power with small numbers of subjects may account for this difference. The broader range of the assay used in this study could also be a contributing factor. It should be noted that serum resistin probably exists as a hexamer (major form) or trimer (a more biologically active form) in mice, which may also affect the assay results (25). The existence of multimers in human serum has recently been implicated (26).

We have shown that plasma resistin was inversely associated with serum HDL cholesterol, independent of age, sex, and BMI. Resistin was reported to be associated with low HDL cholesterol in a smaller numbers of subjects (27,28). Overexpression of resistin in the liver using adenovirus in mice shows enhanced insulin resistance, low serum HDL cholesterol, and high triglyceride levels, which resembles the metabolic syndrome in humans (29). Insulin is known to upregulate lipoprotein lipase, a critical factor producing HDL cholesterol through lipoprotein metabolism. Therefore, insulin resistance caused by elevated plasma resistin could result in reduced serum HDL cholesterol.

We found that plasma resistin was positively associated with hs-CRP. Shetty et al. (28) and McTernan et al. (15) reported that resistin is positively correlated with C-reactive protein (CRP) in a cross-sectional analysis of 77 subjects having diabetes or its risk and 45 type 2 diabetic subjects, respectively. Al-Daghri et al. (30) showed that resistin is associated with CRP in subjects with type 2 diabetes or coronary artery disease in the Saudi Arabian population. Reilly et al. (31) reported that plasma resistin is correlated with inflammatory markers and is predictive of coronary atherosclerosis in humans, independent of CRP. In vitro, resistin increases the expression of critical factors involved in atherosclerotic lesion, such as vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and monocyte chemoattractant protein-1 (32,33). Resistin also enhances human aortic smooth muscle cell proliferation (34). Therefore, resistin could enhance vascular inflammation resulting in elevated serum hs-CRP, whereas an inflammatory cascade has been proposed to lead to hyperresistinemia in humans (35).

In summary, SNP −420 was associated with plasma resistin in the Japanese general population. Plasma resistin was correlated with insulin resistance, lower HDL cholesterol, and high hs-CRP. It is not clear what genetic or environmental factors other than SNP −420, age, and sex affect plasma resistin and how resistin induces insulin resistance in humans. Further studies will be required to clarify these points.

Figure 1—
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1—

Fasting plasma resistin was highest in subjects with the G/G genotype of resistin SNP −420, followed by C/G and C/C in the Japanese general population (n = 2,078). Fasting plasma samples from each subject were measured as described (see research design and methods). A: Fasting plasma resistin increased with an increased number of G allele. Data are means ± SD for each of the SNP −420 genotypes. ANOVA was used for the statistical analyses (F = 368.6, P < 0.0001). The calculated power based on the observed effect and the sample sizes with α = 0.05 was 0.999. Scheffe's test was then used in post hoc analyses, and P < 0.0001 (*). B: The plasma resistin at the peak of the numbers of subjects with each genotype appears to be in the order G/G >C/G > C/C. Number of subjects are calculated for each 2.5 ng/ml range of plasma resistin in each of the SNP −420 genotypes. The range of plasma resistin in which the number of subjects was highest in each genotype was 15–17.5 (G/G), 7.5–10 (C/G), and 5–7.5 ng/ml (C/C).

View this table:
  • View inline
  • View popup
Table 1—

Characteristics of the population studied

View this table:
  • View inline
  • View popup
Table 2—

Age, female sex, SBP, low HDL cholesterol, HOMA-IR, and hs-CRP were correlated with plasma resistin

View this table:
  • View inline
  • View popup
Table 3—

Plasma resistin was correlated with either HOMA-IR, low HDL cholesterol, or hs-CRP, independent of age, sex, and BMI

Acknowledgments

This work was supported by grants for research of metabolic disorders from Ehime University, Kurozumi Medical Foundation, and Astellas Foundation and for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labour and Welfare of Japan; and the Japan Arteriosclerosis Prevention Fund.

We thank M. Murase, T. Nishimiya, Dr. Hashiramoto, and Dr. Takata for suggestions. We also thank C. Hiraoka, A. Murakami, and T. Takasuka for technical assistance.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 23 March 2007. DOI: 10.2337/dc06-1936.

    H.O. and Y.T. contributed equally to this work.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted March 10, 2007.
    • Received September 20, 2006.
  • DIABETES CARE

References

  1. ↵
    Steppan C, Lazar M: The current biology of resistin. J Intern Med 255: 439–447, 2004
    OpenUrlCrossRefPubMedWeb of Science
  2. ↵
    Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 409:307–312, 2001
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    Rangwala S, Rich A, Rhoades B, Shapiro J, Obici S, Rossetti L, Lazar M: Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 53:1937–1941, 2004
    OpenUrlAbstract/FREE Full Text
  4. ↵
    Banerjee R, Rangwala S, Shapiro J, Rich A, Rhoades B, Qi Y, Wang J, Rajala M, Pocai A, Scherer P, Steppan C, Ahima R, Obici S, Rossetti L, Lazar M: Regulation of fasted blood glucose by resistin. Science 303:1195–1198, 2004
    OpenUrlAbstract/FREE Full Text
  5. ↵
    Way JM, Gorgun CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver WR Jr, Willson TM, Kliewer SA, Hotamisligil GS: Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 276:25651–25653, 2001
    OpenUrlAbstract/FREE Full Text
  6. ↵
    DeFronzo RA, Bonadonna RC, Ferrannini E: Pathogenesis of NIDDM: a balanced overview. Diabetes Care 15:318–368, 1992
    OpenUrlAbstract/FREE Full Text
  7. ↵
    McCarthy MI: Progress in defining the molecular basis of type 2 diabetes mellitus through susceptibility-gene identification. Hum Mol Genet 13 Spec No. 1:R33–R41, 2004
    OpenUrlAbstract/FREE Full Text
  8. ↵
    Osawa H, Yamada K, Onuma H, Murakami A, Ochi M, Kawata H, Nishimiya T, Niiya T, Shimizu I, Nishida W, Hashiramoto M, Kanatsuka A, Fujii Y, Ohashi J, Makino H: The G/G genotype of a resistin single-nucleotide polymorphism at −420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3. Am J Hum Genet 75:678–686, 2004
    OpenUrlCrossRefPubMedWeb of Science
  9. ↵
    Osawa H, Onuma H, Ochi M, Murakami A, Yamauchi J, Takasuka T, Tanabe F, Shimizu I, Kato K, Nishida W, Yamada K, Tabara Y, Yasukawa M, Fujii Y, Ohashi J, Miki T, Makino H: Resistin SNP −420 determines its monocyte mRNA and serum levels inducing type 2 diabetes. Biochem Biophys Res Commun 335:596–602, 2005
    OpenUrlPubMedWeb of Science
  10. ↵
    Azuma K, Katsukawa F, Oguchi S, Murata M, Yamazaki H, Shimada A, Saruta T: Correlation between serum resistin level and adiposity in obese individuals. Obes Res 11:997–1001, 2003
    OpenUrlPubMedWeb of Science
  11. ↵
    Cho Y, Youn B, Chung S, Kim K, Lee H, Yu K, Park H, Shin H, Park K: Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans. Diabetologia 47:559–565, 2004
    OpenUrlPubMed
  12. ↵
    Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, Zhu Q, Considine RV: Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 88:5452–5455, 2003
    OpenUrlCrossRefPubMedWeb of Science
  13. ↵
    Fujinami A, Obayashi H, Ohta K, Ichimura T, Nishimura M, Matsui H, Kawahara Y, Yamazaki M, Ogata M, Hasegawa G, Nakamura N, Yoshikawa T, Nakano K, Ohta M: Enzyme-linked immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes. Clin Chim Acta 339:57–63, 2004
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    Lee J, Chan J, Yiannakouris N, Kontogianni M, Estrada E, Seip R, Orlova C, Mantzoros C: Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 88:4848–4856, 2003
    OpenUrlCrossRefPubMedWeb of Science
  15. ↵
    McTernan P, Fisher F, Valsamakis G, Chetty R, Harte A, McTernan C, Clark P, Smith S, Barnett A, Kumar S: Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 88:6098–6106, 2003
    OpenUrlCrossRefPubMedWeb of Science
  16. ↵
    Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 149:331–335, 2003
    OpenUrlAbstract
  17. ↵
    Youn B, Yu K, Park H, Lee N, Min S, Youn M, Cho Y, Park Y, Kim S, Lee H, Park K: Plasma resistin concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 89:150–156, 2004
    OpenUrlCrossRefPubMedWeb of Science
  18. ↵
    Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 365:1415–1428, 2005
    OpenUrlCrossRefPubMedWeb of Science
  19. ↵
    Examination Committee of Criteria for “Obesity Disease” in Japan, Japan Society for the Study of Obesity: New criteria for ‘obesity disease’ in Japan. Circ J 66:987–992, 2002
    OpenUrlCrossRefPubMedWeb of Science
  20. ↵
    Osawa H, Onuma H, Murakami A, Ochi M, Nishimiya T, Kato K, Shimizu I, Fujii Y, Ohashi J, Makino H: Systematic search for single nucleotide polymorphisms in the resistin gene: the absence of evidence for the association of three identified single nucleotide polymorphisms with Japanese type 2 diabetes. Diabetes 51:863–866, 2002
    OpenUrlAbstract/FREE Full Text
  21. ↵
    Ridker PM: High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 103:1813–1818, 2001
    OpenUrlAbstract/FREE Full Text
  22. ↵
    Azuma K, Oguchi S, Matsubara Y, Mamizuka T, Murata M, Kikuchi H, Watanabe K, Katsukawa F, Yamazaki H, Shimada A, Saruta T: Novel resistin promoter polymorphisms: association with serum resistin level in Japanese obese individuals. Horm Metab Res 36:564–570, 2004
    OpenUrlCrossRefPubMed
  23. ↵
    Smith S, Bai F, Charbonneau C, Janderova L, Argyropoulos G: A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 52:1611–1618, 2003
    OpenUrlAbstract/FREE Full Text
  24. ↵
    Silha JV, Krsek M, Hana V, Marek J, Jezkova J, Weiss V, Murphy LJ: Perturbations in adiponectin, leptin and resistin levels in acromegaly: lack of correlation with insulin resistance. Clin Endocrinol (Oxf) 58:736–742, 2003
    OpenUrlCrossRefPubMed
  25. ↵
    Patel S, Rajala M, Rossetti L, Scherer P, Shapiro L: Disulfide-dependent multimeric assembly of resistin family hormones. Science 304:1154–1158, 2004
    OpenUrlAbstract/FREE Full Text
  26. ↵
    Gerber M, Boettner A, Seidel B, Lammert A, Bar J, Schuster E, Thiery J, Kiess W, Kratzsch J: Serum resistin levels of obese and lean children and adolescents: biochemical analysis and clinical relevance. J Clin Endocrinol Metab 90:4503–4509, 2005
    OpenUrlCrossRefPubMedWeb of Science
  27. ↵
    Chen CC, Li TC, Li CI, Liu CS, Wang HJ, Lin CC: Serum resistin level among healthy subjects: relationship to anthropometric and metabolic parameters. Metabolism 54:471–475, 2005
    OpenUrlCrossRefPubMedWeb of Science
  28. ↵
    Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A: Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 27:2450–2457, 2004
    OpenUrlAbstract/FREE Full Text
  29. ↵
    Sato N, Kobayashi K, Inoguchi T, Sonoda N, Imamura M, Sekiguchi N, Nakashima N, Nawata H: Adenovirus-mediated high expression of resistin causes dyslipidemia in mice. Endocrinology 146:273–279, 2005
    OpenUrlCrossRefPubMedWeb of Science
  30. ↵
    Al-Daghri N, Chetty R, McTernan PG, Al-Rubean K, Al-Attas O, Jones AF, Kumar S: Serum resistin is associated with C-reactive protein & LDL cholesterol in type 2 diabetes and coronary artery disease in a Saudi population. Cardiovasc Diabetol 4:10–15, 2005
    OpenUrlCrossRefPubMed
  31. ↵
    Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ: Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111:932–939, 2005
    OpenUrlAbstract/FREE Full Text
  32. ↵
    Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, Manabe I, Utsunomiya K, Nagai R: Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun 314:415–419, 2004
    OpenUrlCrossRefPubMedWeb of Science
  33. ↵
    Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, Mickle DA: Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 108:736–740, 2003
    OpenUrlAbstract/FREE Full Text
  34. ↵
    Calabro P, Samudio I, Willerson JT, Yeh ET: Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation 110:3335–3340, 2004
    OpenUrlAbstract/FREE Full Text
  35. ↵
    Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA: An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med 1:161–168, 2004
    OpenUrlWeb of Science
PreviousNext
Back to top
Diabetes Care: 30 (6)

In this Issue

June 2007, 30(6)
  • Table of Contents
  • About the Cover
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Plasma Resistin, Associated With Single Nucleotide Polymorphism −420, Is Correlated With Insulin Resistance, Lower HDL Cholesterol, and High-Sensitivity C-Reactive Protein in the Japanese General Population
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Plasma Resistin, Associated With Single Nucleotide Polymorphism −420, Is Correlated With Insulin Resistance, Lower HDL Cholesterol, and High-Sensitivity C-Reactive Protein in the Japanese General Population
Haruhiko Osawa, Yasuharu Tabara, Ryuichi Kawamoto, Jun Ohashi, Masaaki Ochi, Hiroshi Onuma, Wataru Nishida, Kazuya Yamada, Jun Nakura, Katsuhiko Kohara, Tetsuro Miki, Hideichi Makino
Diabetes Care Jun 2007, 30 (6) 1501-1506; DOI: 10.2337/dc06-1936

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Plasma Resistin, Associated With Single Nucleotide Polymorphism −420, Is Correlated With Insulin Resistance, Lower HDL Cholesterol, and High-Sensitivity C-Reactive Protein in the Japanese General Population
Haruhiko Osawa, Yasuharu Tabara, Ryuichi Kawamoto, Jun Ohashi, Masaaki Ochi, Hiroshi Onuma, Wataru Nishida, Kazuya Yamada, Jun Nakura, Katsuhiko Kohara, Tetsuro Miki, Hideichi Makino
Diabetes Care Jun 2007, 30 (6) 1501-1506; DOI: 10.2337/dc06-1936
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • RESEARCH DESIGN AND METHODS
    • RESULTS
    • CONCLUSIONS
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Tables
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort
  • Day-to-Day Variations in Fasting Plasma Glucose Do Not Influence Gastric Emptying in Subjects With Type 1 Diabetes
  • High Prevalence of Advanced Liver Fibrosis Assessed by Transient Elastography Among U.S. Adults With Type 2 Diabetes
Show more Pathophysiology/Complications

Similar Articles

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.