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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 7 2835-2839
Copyright © 2007 by The Endocrine Society

BRIEF REPORT

Relationships of Plasma Adiponectin Level and Adiponectin Receptors 1 and 2 Gene Expression to Insulin Sensitivity and Glucose and Fat Metabolism in Monozygotic and Dizygotic Twins

Heidi Storgaard1, Pernille Poulsen1, Charlotte Ling, Leif Groop and Allan A. Vaag

Steno Diabetes Center (H.S., P.P., A.A.V.), 2820 Gentofte, Denmark; and Department of Clinical Sciences/Diabetes and Endocrinology (C.L., L.G.), Lund University, Clinical Research Centre, University Hospital Malmö, S-205 02 Malmö, Sweden

Address all correspondence and requests for reprints to: Pernille Poulsen, Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. E-mail: pepn{at}steno.dk.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Adiponectin is a key insulin-sensitizing adipokine acting on muscle metabolism via two specific receptors [adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2, respectively)].

Objectives: The aim of the study was to investigate the genetic and nongenetic control of plasma adiponectin and muscle AdipoR1/R2 gene expression and the impact of these components on in vivo glucose and fat metabolism.

Design and Participants: Plasma adiponectin and muscle gene expression of AdipoR1/R2 were measured before and during insulin infusion in 89 young and 69 elderly monozygotic and dizygotic twins. Insulin action, and glucose and fat oxidation rates were determined using hyperinsulinemic euglycemic clamps and indirect calorimetry.

Results: We demonstrated a genetic component in the control of plasma adiponectin and AdipoR1/R2 gene expression. Furthermore, levels of adiponectin and AdipoR1/R2 were influenced by age, sex, abdominal obesity, and aerobic capacity. Intrapair correlations in monozygotic twins indicated a nongenetic influence of birth weight on plasma adiponectin and AdipoR2 expression. Nonoxidative glucose metabolism was associated with AdipoR1 and plasma adiponectin, in young and elderly twins, respectively. In addition, plasma adiponectin was related to glucose and fat oxidation in younger subjects.

Conclusions: Plasma adiponectin and muscle gene expression of its specific receptors are controlled by genetic and several specific nongenetic factors. The data suggest that the "adiponectin axis" plays a role in in vivo insulin action and nonoxidative glucose metabolism.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
HIGH LEVELS OF circulating adiponectin are associated with improved insulin sensitivity (1) and a reduced risk of type 2 diabetes (T2D) (2, 3, 4). Two receptors for adiponectin, termed adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2, respectively) have been described (5), and are highly expressed in human skeletal muscle (6, 7) and pancreatic ß-cells (8). Nevertheless, the specific role of AdipoR1 and AdipoR2 in glucose metabolism in diabetic and prediabetic subjects is unclear. AdipoR1 mRNA levels in skeletal muscle cells from young healthy subjects correlated positively with insulin secretion, but not with insulin sensitivity (9). A positive correlation between insulin sensitivity and the expression of both receptors in skeletal muscle was found in first-degree relatives of T2D patients (6). Other studies have demonstrated normal (9, 10) or increased muscle expression (7) of both receptors in T2D patients relative to glucose-tolerant subjects. However, several of these previous studies were small, and the metabolic phenotypes were insufficiently determined.

Genetic factors and several nongenetic factors, including age, physical inactivity, obesity, and low birth weight, contribute to the risk of T2D. The influence of these factors on adiponectin and its receptor levels remains to be determined. Twin studies are instrumental in quantifying the extent to which a phenotype is determined by genetic and nongenetic factors. Furthermore, measuring correlations between within-twin pair differences in monozygotic (MZ) twins allows associations of genetic and nongenetic origin to be distinguished.

This study aimed to investigate the relative influence of genetic and nongenetic factors [age, sex, birth weight, obesity, and aerobic capacity (VO2max)] on plasma adiponectin and the expression of AdipoR1/R2 in skeletal muscle before and during insulin stimulation, as well as the impact of this "adiponectin axis" on glucose and fat metabolism, measured by "gold standard" techniques in a cohort of young and elderly MZ and dizygotic (DZ) twins (11, 12).


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Young (n = 89) and elderly (n = 69) same-sex MZ and DZ healthy twins underwent a 2-h (40 mU/m2/min) hyperinsulinemic euglycemic clamp, including indirect calorimetry, as previously described (11, 12, 13). Muscle biopsies were obtained from the vastus lateralis muscle before and during insulin infusion as previously described (11). The present study was approved by the regional Ethical Committees and conducted in accordance with the Helsinki Declaration.

Analytical methods

Fasting levels of plasma adiponectin were determined by ELISA (Linco Research, St. Charles, MO). The intraassay coefficient of variation was 4.3% (n = 12). AdipoR1 and R2 mRNA levels were quantified using TaqMan real-time PCR with an ABI 7900 system (Applied Biosystems, Foster City, CA), and gene-specific probes and primer pairs for AdipoR1 (Assays-on-demand, Hs00360422_m1; Applied Biosystems) and AdipoR2 (Assays-on-demand, Hs00226105_m1; Applied Biosystems). The transcript quantities of AdipoR1 and R2 were normalized to the mRNA level of cyclophilin A (4326316E), and expressed as arbitrary units (AUs).

Statistical methods

Comparisons between young/elderly and male/female subjects were performed using the "proc mixed" (ANOVA) procedure in SAS (version 8.2; SAS Institute Inc., Cary, NC), with adjustment for intratwin pair relationships (11). Data are presented as mean (SD). Absolute phenotypic correlations (Spearman) were calculated using SigmaStat 3.0 (Systat Software, Inc., San Jose, CA).

Intratwin-pair correlations between differences in phenotypic variables within MZ and DZ twin pairs (i.e. twin A - twin B) allow adjustment for the influence of common environmental and maternal factors, and, in particular, for genotype in MZ twins. Accordingly, a significant intratwin-pair correlation within MZ twins (regardless of the correlation in DZ twins) is of nongenetic origin, while a significant correlation only among DZ twins suggests a genetic origin. The correlation analyses were performed using SigmaStat 3.0.

The total phenotypic variance is the sum of the variance attributable to effects of both genetic and environmental factors. The heritability (h2) expresses the proportion of variance attributable to genetic variance, and was assessed by biometric modeling as previously described (13).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Clinical characteristics

The clinical characteristics of the subjects have been described previously (11, 12, 13). In brief, the elderly [age 62.4 yr (0.2)] twins had greater total fat mass, higher trunk-leg fat ratios, and a higher level of fat oxidation (FOX), but lower VO2max, insulin-stimulated whole-body glucose uptake (glucose disposal rate), glucose oxidation (GOX), and nonoxidative glucose metabolism (NOGM) than the younger [age 28.0 yr (0.2)] twins.

The relationship between plasma adiponectin and muscle AdipoR1/R2 gene expression levels, and effect of age and insulin

AdipoR1 gene expression was similar in young and elderly twins. The expression of basal (P < 0.001) and clamp (P < 0.001) AdipoR2 was lower in elderly than in young twins. Insulin increased the expression of AdipoR2 significantly in both elderly and young twins, whereas AdipoR1 expression was not affected by insulin. Fasting plasma adiponectin values were significantly higher in elderly than in young twins (P < 0.001) (Table 1Go).


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  		TABLE 1. AdipoR1 and AdipoR2 mRNA expression (AU) and plasma adiponectin (mg/liter) in young (n = 89) and elderly (n = 69) twins during basal and insulin-stimulated steady-state periods

 
Levels of AdipoR1 and AdipoR2 mRNA during both steady-state periods were positively correlated in young and elderly subjects (Table 2Go). Plasma adiponectin was inversely correlated with AdipoR1 and AdipoR2 in young but not in elderly twins.


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  		TABLE 2. Correlation coefficients between AdipoR1 and AdipoR2 mRNA expression (AU) and plasma adiponectin (mg/liter) in young (bottom left) and elderly (upper right) twins during basal and insulin-stimulated steady-state periods

 
Factors influencing plasma adiponectin and muscle AdipoR1/R2 expression levels

Plasma adiponectin levels were significantly higher in females than males [mean (SD), mg/liter; males: 6.9 (3.8); females: 10.0 (4.1); P < 0.001], regardless of age. In contrast, men had higher AdipoR1 and AdipoR2 mRNA levels than women during both steady-state periods [mean (SD), AU; AdipoR1basal: 0.64 (0.23) vs. 0.50 (0.25), P < 0.001; AdipoR1insulin: 0.67 (0.25) vs. 0.46 (0.13), P < 0.001; AdipoR2basal: 0.44 (0.14) vs. 0.37 (0.09), P < 0.001; and AdipoR2insulin: 0.48 (0.15) vs. 0.39 (0.10), P < 0.001].

AdipoR1 mRNA level was positively associated with VO2max (basal: r = 0.41, P < 0.001; insulin: r = 0.30, P = 0.005) and trunk-leg fat ratio (basal: r = 0.40, P < 0.001; insulin: r = 0.34, P = 0.001) and negatively associated with total fat percentage (basal: r = –0.52, P < 0.001; insulin: r = –0.39, P < 0.001) in young subjects. In the elderly, AdipoR1 mRNA level was weakly associated with trunk-leg fat ratio (insulin: r = 0.27, P = 0.02).

AdipoR2 mRNA level was negatively associated with total fat percentage (basal: r = –0.31, P = 0.003; insulin: r = 0.31, P = 0.004) and positively associated with VO2max (basal: r = 0.21, P = 0.05) and trunk-leg fat ratio (r = 0.27, P = 0.01). In the elderly, AdipoR2 mRNA level was not associated with measures of VO2max or body composition.

Plasma adiponectin was negatively correlated with trunk-leg fat ratio in both age groups (young: r = –0.54, P < 0.0.001; elderly: r = –0.48, P < 0.0001) and positively associated with total fat percentage in the young (r = 0.38; P < 0.001).

h2 of plasma adiponectin and muscle AdipoR1/R2 expression levels

The h2 estimates suggest that there is a major genetic component of plasma adiponectin and AdipoR1/R2 gene expression in both young (adiponectin: h2 = 76%, AdipoR1; basal: h2 = 66%, insulin: h2 = 75%, AdipoR2; and basal: h2 = 73%, insulin: h2 = 64%) and elderly (adiponectin: h2 = 58%, AdipoR1; basal: h2 = 78%, insulin: h2 = 74%, AdipoR2; and basal: h2 = 77%, insulin: h2 = 39%) twins.

Impact of birth weight on plasma adiponectin and muscle AdipoR1/R2 gene expression levels

When performing intrapair correlations, eliminating a genetic influence in MZ twins, we demonstrated a positive correlation between plasma adiponectin and birth weight in young MZ twins (r = 0.37; P = 0.007), but not in DZ or elderly twins. We found a positive intrapair correlation between clamp AdipoR1 gene expression and birth weight in DZ (r = 0.41; P = 0.012), but not in MZ (r = 0.17; nonsignificant) elderly twins. Furthermore, in elderly twins there was a significant intrapair correlation between clamp AdipoR2 gene expression and birth weight (MZ: r = 0.36, P = 0.037; DZ: r = 0.35, P = 0.031).

Impact of adiponectin and its receptors on glucose and fat metabolism

Plasma adiponectin was associated with FOX (r = –0.23; P = 0.03) and GOX (r = 0.37; P < 0.001) in young twins, and positively associated with glucose disposal rate (r = 0.67; P < 0.001) and NOGM (r = 0.72; P < 0.001) in elderly twins. AdipoR1 gene expression was positively associated with NOGM (r = 0.24; P = 0.02) only in young twins. No associations were demonstrated between AdipoR2 gene expression and metabolic variables in either age group.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study provides evidence of a strong genetic influence on circulating adiponectin and muscle AdipoR1/R2 gene expression in both young and elderly twins, with h2 estimates ranging from 39–78%. This is consistent with the finding that variation in the adiponectin gene is associated with variation in plasma adiponectin levels, obesity, insulin resistance, and T2D (14). Furthermore, single nucleotide polymorphisms of the genes encoding AdipoR1 and AdipoR2 have been associated with T2D (15, 16) and insulin resistance (17, 18). This study supports the idea of a genetically controlled "adiponectin axis" that plays some role in the pathophysiology of insulin resistance and T2D.

Interestingly, we found an influence of age on the levels and relationship of adiponectin with its receptors. In younger subjects, adiponectin was inversely correlated with levels of AdipoR1/R2, consistent with findings from middle-aged subjects (7). However, no such association was seen in the elderly twins. Higher plasma adiponectin levels and lower AdipoR2 mRNA expression were observed in elderly than in younger twins. The higher adiponectin level, which is a key determinant of glucose metabolism in elderly subjects, may represent an effect that compensates for the reduction of receptor levels and/or "adiponectin resistance" with increasing age.

In the young twins, AdipoR1 expression was associated with NOGM, and adiponectin was associated negatively with FOX and positively with GOX. In elderly twins, glucose disposal and NOGM were associated with circulating adiponectin, which implies a role for adiponectin in the control of muscle glycogen synthesis in elderly subjects (19). However, receptor expression levels were not associated with any metabolic variables. Thus, the relative influence of adiponectin and its specific receptors on in vivo insulin action seems to change with age. The lack of association between plasma adiponectin and glucose metabolism in the young is somewhat surprising. One explanation for this may be that young subjects are lean and insulin sensitive, and the association between adiponectin and insulin resistance may very well develop later in the course of becoming increasingly obese and insulin resistant (20). It could also be explained by an age-related change in the ratio of high-molecular weight adiponectin to total adiponectin, which has recently been suggested to be a better indicator of metabolic activity (21).

The role of AdipoR1/R2 in the regulation of glucose metabolism is controversial, with reports of positive and negative associations (6, 7, 9). These apparently paradoxical results may be a consequence of using different methods to measure insulin action, the size of the study populations, glucose tolerance, and, perhaps, as the results of this study suggest in particular, age. Importantly, in this large and thoroughly characterized study population, where in vivo insulin action was measured by the "gold standard" hyperinsulinemic clamp technique, we found indication of a specific role for the muscle AdipoR1 in the control of insulin action and NOGM in young but not elderly subjects. The age dependency of the influence of AdipoR1 expression level and, in particular, the absence of any distinct effect of muscle AdipoR2 expression level on in vivo insulin action requires further investigation. Regardless, the present results suggest that these two receptors could mediate differential cellular responses to adiponectin within and between tissues.

Plasma adiponectin was negatively associated with abdominal obesity, which is consistent with previous findings (7). Expression levels of AdipoR1 and AdipoR2 were, on the other hand, positively associated with trunk-leg ratio. A positive effect of acute and chronic training on AdipoR1 and AdipoR2 expression in skeletal muscle (7) has recently been reported, and is consistent with the positive association between VO2max and AdipoR1 and AdipoR2 in the present study. The higher plasma adiponectin level in females than in males is consistent with previous findings in young (22) and elderly (23) subjects, whereas a concomitant reduction of the receptor expression level has not been demonstrated before, to our knowledge.

Recent studies suggest that reduced levels of adiponectin may play an important role in insulin resistance associated with reduced fetal growth (24). Performing intrapair correlations, and eliminating any genetic influence in MZ twins, we demonstrated positive associations between birth weight and plasma adiponectin in young, and between birth weight and AdipoR2 expression in elderly MZ twins, indicating nongenetic associations. We recently showed that low birth weight is nongenetically associated with insulin resistance in elderly but not in young MZ twins (12). The association between plasma adiponectin and birth weight in young, but not in elderly twins, suggests that reduced plasma adiponectin levels may, to some extent, precede overt insulin resistance in elderly twins, but the "adiponectin axis" per se does not fully explain the nongenetic impact of birth weight on insulin action in elderly twins.

Although many statistical analyses were performed in this study, all were based upon a priori hypotheses, and correction for multiple testing was, therefore, not performed in the primary analysis. Regardless, it may be important to realize that the major findings in this study, including the interrelationship between circulating adiponectin and the expression of its receptors, the effect of age and gender on AdipoR1/R2 expression and adiponectin, and the association between adiponectin and glucose and FOX in the young, and adiponectin and nonoxidative glucose metabolism in the elderly, all remained statistically significant even after applying Bonferroni correction for multiple testing.

In conclusion, we have found evidence for a strong genetic component in the control of plasma adiponectin and muscle AdipoR1/R2 gene expression levels in twins. In addition, nongenetic factors, including age, sex, birth weight, abdominal obesity, and VO2max, influence the adiponectin-AdipoR1/R2 axis. Levels of AdipoR1, but not AdipoR2, gene expression in skeletal muscle and plasma adiponectin are related to nonoxidative glucose metabolism in young and elderly subjects, respectively.


   Acknowledgments
 
We thank Emma Nilsson, Margareta Svensson, and Marianne Modest for their excellent technical assistance.


   Footnotes
 
This investigation was funded by the following foundations: Region Skåne, Swedish Research Council, Novo Nordisk, Danish Medical Research Council, Danish Diabetes Foundation, Exgenesis Grant 005272 from the European Union, Malmö University Hospital, Swegene, the Diabetes Programe at Lund University, Hedlund, Bergvall, and Lungberg.

Disclosure Statement: H.S., P.P., and C.L. have nothing to declare. L.G. has been a consultant for and served on advisory boards for Aventis-Sanofi, Bristol Myers Squibb, GlaxoSmithKline and Roche. A.A.V. has been a consultant for and served on advisory boards for Novo Nordisk.

First Published Online April 10, 2007

1 H.S. and P.P. contributed equally to this work. Back

Abbreviations: AdipoR, Adiponectin receptor; AU, arbitrary unit; DZ, dizygotic; FOX, fat oxidation; GOX, glucose oxidation; h2, heritability; MZ, monozygotic; NOGM, nonoxidative glucose metabolism; T2D, type 2 diabetes; VO2max, aerobic capacity.

Received August 17, 2006.

Accepted April 3, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T 2001 The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946[CrossRef][Medline]
  2. Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, Knowler WC, Krakoff J 2002 Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360:57–58[CrossRef][Medline]
  3. Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF 2003 Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228[CrossRef][Medline]
  4. Duncan BB, Schmidt MI, Pankow JS, Bang H, Couper D, Ballantyne CM, Hoogeveen RC, Heiss G 2004 Adiponectin and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 53:2473–2478[Abstract/Free Full Text]
  5. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T 2003 Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–769[CrossRef][Medline]
  6. Civitarese AE, Jenkinson CP, Richardson D, Bajaj M, Cusi K, Kashyap S, Berria R, Belfort R, DeFronzo RA, Mandarino LJ, Ravussin E 2004 Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type 2 diabetes. Diabetologia 47:816–820[CrossRef][Medline]
  7. Bluher M, Bullen Jr JW, Lee JH, Kralisch S, Fasshauer M, Kloting N, Niebauer J, Schon MR, Williams CJ, Mantzoros CS, Blüher M 2006 Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training. J Clin Endocrinol Metab 91:2310–2316[Abstract/Free Full Text]
  8. Kharroubi I, Rasschaert J, Eizirik DL, Cnop M 2003 Expression of adiponectin receptors in pancreatic ß cells. Biochem Biophys Res Commun 312:1118–1122[CrossRef][Medline]
  9. Staiger H, Kaltenbach S, Staiger K, Stefan N, Fritsche A, Guirguis A, Peterfi C, Weisser M, Machicao F, Stumvoll M, Haring HU 2004 Expression of adiponectin receptor mRNA in human skeletal muscle cells is related to in vivo parameters of glucose and lipid metabolism. Diabetes 53:2195–2201[Abstract/Free Full Text]
  10. Debard C, Laville M, Berbe V, Loizon E, Guillet C, Morio-Liondore B, Boirie Y, Vidal H 2004 Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients. Diabetologia 47:917–925[CrossRef][Medline]
  11. Storgaard H, Poulsen P, Ling C, Groop L, Vaag AA 2006 Human skeletal muscle GLUT4 mRNA levels in twins–influence of genetic and environmental factors. J Clin Endocrinol Metab 91:702–708[Abstract/Free Full Text]
  12. Poulsen P, Vaag A 2006 The intrauterine environment as reflected by birth size and twin and zygosity status influences insulin action and intracellular glucose metabolism in an age- or time-dependent manner. Diabetes 55:1819–1825[Abstract/Free Full Text]
  13. Poulsen P, Levin K, Petersen I, Christensen K, Beck-Nielsen H., Vaag A 2005 Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins. Diabetes 54:275–283[Abstract/Free Full Text]
  14. Vasseur F, Lepretre F, Lacquemant C, Froguel P 2003 The genetics of adiponectin. Curr Diab Rep 3:151–158[Medline]
  15. Damcott CM, Ott SH, Pollin TI, Reinhart LJ, Wang J, O’connell JR, Mitchell BD, Shuldiner AR 2005 Genetic variation in adiponectin receptor 1 and adiponectin receptor 2 is associated with type 2 diabetes in the Old Order Amish. Diabetes 54:2245–2250[Abstract/Free Full Text]
  16. Vaxillaire M, Dechaume A, Vasseur-Delannoy V, Lahmidi S, Vatin V, Lepretre F, Boutin P, Hercberg S, Charpentier G, Dina C, Froguel P 2006 Genetic analysis of ADIPOR1 and ADIPOR2 candidate polymorphisms for type 2 diabetes in the Caucasian population. Diabetes 55:856–861[Abstract/Free Full Text]
  17. Wang H, Zhang H, Jia Y, Zhang Z, Craig R, Wang X, Elbein SC 2004 Adiponectin receptor 1 gene (ADIPOR1) as a candidate for type 2 diabetes and insulin resistance. Diabetes 53:2132–2136[Abstract/Free Full Text]
  18. Stefan N, Machicao F, Staiger H, Machann J, Schick F, Tschritter O, Spieth C, Weigert C, Fritsche A, Stumvoll M, Haring HU 2005 Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat. Diabetologia 48:2282–2291[CrossRef][Medline]
  19. Hojlund K, Frystyk J, Levin K, Flyvbjerg A, Wojtaszewski JF, Beck-Nielsen H 2006 Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes. Diabetologia 49:1283–1291[CrossRef][Medline]
  20. Kantartzis K, Fritsche A, Tschritter O, Thamer C, Haap M, Schafer S, Stumvoll M, Haring HU, Stefan N 2005 The association between plasma adiponectin and insulin sensitivity in humans depends on obesity. Obes Res 13:1683–1691[Medline]
  21. Fisher FF, Trujillo ME, Hanif W, Barnett AH, McTernan PG, Scherer PE, Kumar S 2005 Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia 48:1084–1087[CrossRef][Medline]
  22. Zoico E, Di Francesco V, Mazzali G, Vettor R, Fantin F, Bissoli L, Guariento S, Bosello O, Zamboni M 2004 Adipocytokines, fat distribution, and insulin resistance in elderly men and women. J Gerontol A Biol Sci Med Sci 59:M935–M939
  23. Punthakee Z, Delvin EE, O’loughlin J, Paradis G, Levy E, Platt RW, Lambert M 2006 Adiponectin, adiposity, and insulin resistance in children and adolescents. J Clin Endocrinol Metab 91:2119–2125[Abstract/Free Full Text]
  24. Jaquet D, Deghmoun S, Chevenne D, Czernichow P, Levy-Marchal C 2006 Low serum adiponectin levels in subjects born small for gestational age: impact on insulin sensitivity. Int J Obes 30:83–87[CrossRef][Medline]




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