Download PDF
Exp Clin Endocrinol Diabetes 2016; 124(09): 541-547
DOI: 10.1055/s-0042-109262
Article
© Georg Thieme Verlag KG Stuttgart · New York

Reduction Levels and the Effects of High-Molecular-Weight Adiponectin via AMPK/eNOS in Chinese Type 2 Diabetes

K. Lian   *
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
X. Guo   *
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
Q. Huang
2   Department of Endocrinology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
3   Department of Endocrinology, No.323 Hospital of People’s Liberation Army, Xi’an, China”
,
Z. Tan
4   Department of Health Statistics, Fourth Military Medical University, Xi’an, China
,
C. Xia
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
R. Wang
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
F. Yi
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
W. Li
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
J. Liu
5   Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
Y. Li
6   Health Examination Center, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
S. Guo
7   Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
H. Wang
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
Q. Ji
2   Department of Endocrinology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
,
L. Tao
1   Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
› Author Affiliations
Further Information

Publication History

received 04 March 2016
first decision 12 May 2016

accepted 25 May 2016

Publication Date:
20 July 2016 (online)

Also available at
    Permissions and Reprints

Abstract

Aim: This study was to investigate the change of high-molecula-weight (HMW) adiponectin (APN) isoform, the association between type 2 diabetes mellitus (T2DM) and HMW APN isoform, the variation of Disulfide-bond A oxidoreductase-like protein (DsbA-L), the effect of HMW APN isoform on AMP-dependent protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) in Chinese T2DM.

Method: 169 patients aged at (48.7±9.4) years and 107 healthy control subjects aged at (42.6±7.8) years took part in this study. Anthropometric measures of the characters were assayed and different APN isoforms, DsbA-L, AMPK and eNOS levels were determined.

Results: Ln(sRAGE) and Ln(Adiponectin) were significantly lower and significantly higher for the other characteristics in T2DM. Ln(Adiponectin) was negatively and significantly correlated with WHR, Ln(triglycerides), fasting plasma glucose, HbA1c (%) in control subjects and T2DM patients. Plasma and adipose tissue total APN and HMW APN were significantly reduced in newly diagnosed T2DM patients. DsbA-L was markedly down-regulated in diabetic adipose tissue. HMW APN caused significant decreases in AMPK and eNOS phosphorylation levels of human umbilical vein endothelial cells (HUVECs).

Conclusions: Our results demonstrated that total APN levels was closely related to the risk of T2DM and HMW APN reduction was involved in the diabetic vascular AMPK/eNOS signal pathway. The findings will provide insight into novel therapeutic approaches for reducing the elevated cardiovascular risk associated with T2DM.

Key words

HMW adiponectin - DsbA-L - AMPK/eNOS - diabetes

* These authors contributed equally to this paper.


 

  • References

  • 1 Chang Y, Guo X, Chen Y et al. A body shape index and body roundness index: two new body indices to identify diabetes mellitus among rural populations in northeast China. BMC Public Health 2015; 15: 794
    CrossrefPubMedGoogle Scholar
  • 2 Duan JG, Chen XY, Wang L et al. Sex differences in epidemiology and risk factors of acute coronary syndrome in Chinese patients with type 2 diabetes: a long-term prospective cohot study. PLoS One 2015; 10: e0122031
    CrossrefPubMedGoogle Scholar
  • 3 Qi L, Feng L, Ding X et al. Prevalence of diabetes and impaired fasting glucose among residents in the Three Gorges Reservoir Region, China. BMC Public Health 2014; 14: 1152
    CrossrefPubMedGoogle Scholar
  • 4 Chakraborti CK. Role of adiponectin and some other factors linking type 2 diabetes mellitus and obesity. World J Diabetes 2015; 6: 1296-1308
    CrossrefPubMedGoogle Scholar
  • 5 Soleimani M. Insulin resistance and hypertension: new insights. Kidney Int 2015; 87: 497-499
    CrossrefPubMedGoogle Scholar
  • 6 Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia 2012; 55: 2319-2326
    CrossrefPubMedGoogle Scholar
  • 7 Matsuda M, Shimomura I. Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord 2014; 15: 1-10
    CrossrefPubMedGoogle Scholar
  • 8 Yamauchi T, Kamon J, Waki H et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941-946
    CrossrefPubMedGoogle Scholar
  • 9 Peake PW, Kriketos AD, Campbell LV et al. The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur J Endocrinol 2005; 153: 409-417
    CrossrefPubMedGoogle Scholar
  • 10 Shetty S, Kusminski CM, Scherer PE. Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. Trends Pharmacol Sci 2009; 30: 234-239
    CrossrefPubMedGoogle Scholar
  • 11 Hanley AJ, Wagenknecht LE, Norris JM et al. Adiponectin and the incidence of type 2 diabetes in Hispanics and African Americans: the IRAS Family Study. Diabetes Care 2011; 34: 2231-2236
    CrossrefPubMedGoogle Scholar
  • 12 Pajvani UB, Hawkins M, Combs TP et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279: 12152-12162
    CrossrefPubMedGoogle Scholar
  • 13 Heidemann C, Sun Q, van Dam RM et al. Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann Intern Med 2008; 149: 307-316
    CrossrefPubMedGoogle Scholar
  • 14 Zhu N, Pankow JS, Ballantyne CM et al. High-molecular-weight adiponectin and the risk of type 2 diabetes in the ARIC study. J Clin Endocrinol Metab 2010; 95: 5097-5104
    CrossrefPubMedGoogle Scholar
  • 15 Krzyzanowska K, Aso Y, Mittermayer F et al. High-molecular-weight adiponectin does not predict cardiovascular events in patients with type 2 diabetes. Trans Res 2009; 153: 199-203
    CrossrefPubMedGoogle Scholar
  • 16 Jin D, Sun J, Huang J et al. Peroxisome proliferator-activated receptor γ enhances adiponectin secretion via up-regulating DsbA-L expression. Mol Cell Endocrinol 2015; 411: 97-104
    CrossrefPubMedGoogle Scholar
  • 17 Liu M, Zhou L, Xu A et al. A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization. Proc Natl Acad Sci USA 2008; 105: 18302-18307
    CrossrefPubMedGoogle Scholar
  • 18 Liu M, Xiang R, Wilk SA et al. Fat-specific DsbA-L overexpression promotes adiponectin multimerization and protects mice from diet-induced obesity and insulin resistance. Diabetes 2012; 61: 2776-2786
    CrossrefPubMedGoogle Scholar
  • 19 Cho YS, Chen CH, Hu C et al. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nat Genet 2012; 44: 67-72
    PubMedGoogle Scholar
  • 20 Zhang L, Li MM, Corcoran M et al. Cooper GJS. Essential roles of insulin, AMPK signaling and lysyl and prolyl hydroxylases in the biosynthesis and multimerization of adiponectin. Mol Cell Endocrinol 2015; 399: 164-177
    CrossrefPubMedGoogle Scholar
  • 21 Niemann B, Pan R, Teschner M et al. Age and obesity-associated changes in the expression and activation of components of the AMPK signaling pathway in human right atrial tissue. Exp Gerontol 2013; 48: 55-63
    CrossrefPubMedGoogle Scholar
  • 22 Kobayashi H, Ouchi N, Kihara S et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circul Res 2004; 94: e27-e31
    CrossrefPubMedGoogle Scholar
  • 23 Lee CH, Lee SD, Ou HC et al. Eicosapentaenoic acid protects against palmitic acid-induced endothelial dysfunction via activation of the AMPK/eNOS pathway. Int J Mol Sci 2014; 15: 10334-10349
    CrossrefPubMedGoogle Scholar
  • 24 Duplain H, Burcelin R, Sartori C et al. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 2001; 104: 342-345
    CrossrefPubMedGoogle Scholar
  • 25 Wu X, Mahadev K, Fuchsel L et al. Adiponectin suppresses IkappaB kinase activation induced by tumor necrosis factor-alpha or high glucose in endothelial cells: role of cAMP and AMP kinase signaling. Am J Physiol Endocrinol Metab 2007; 293: E1836-E1844
    CrossrefPubMedGoogle Scholar
  • 26 Jalovaara K, Santaniemi M, Timonen M et al. Low serum adiponectin level as a predictor of impaired glucose regulation and type 2 diabetes mellitus in a middle-aged Finnish population. Metabolism 2008; 57: 1130-1134
    CrossrefPubMedGoogle Scholar
  • 27 Su SC, Pei D, Hsieh CH et al. Circulating pro-inflammatory cytokines and adiponectin in young men with type 2 diabetes. Acta Diabetol 2011; 48: 113-119
    CrossrefPubMedGoogle Scholar
  • 28 Kim HY, Bae EH, Ma SK et al. Association of serum adiponectin level with albuminuria in chronic kidney disease patients. Clin Exp Nephrol 2015; DOI: 10.1007/s10157-015-1173-4.
    PubMedGoogle Scholar
  • 29 Kumpatla S, Karuppiah K, Immaneni S et al Comparison of plasma adiponectin & certain inflammatory markers in angiographically proven coronary arterydisease patients with & without diabetes – a study from India. Indian J Med Res 2014; 139: 841-850
    PubMedGoogle Scholar
  • 30 Li R, Xu M, Wang X et al. Reduced vascular responsiveness to adiponectin in hyperlipidemic rats – mechanisms and significance. J Mol Cell Cardiol 2010; 49: 508-515
    CrossrefPubMedGoogle Scholar
  • 31 Silva TE, Colombo G, Schiavon LL. Adiponectin: a multitasking player in the field of liver diseases. Diabetes Metab 2014; 40: 95-107
    CrossrefPubMedGoogle Scholar
  • 32 Kadowaki T, Yamauchi T, Kubota N et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006; 116: 1784-1792
    CrossrefPubMedGoogle Scholar
  • 33 Trujillo ME, Scherer PE. Adiponectin – journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med 2005; 257: 167175
    PubMedGoogle Scholar
  • 34 Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 2006; 55: 1537-1545
    CrossrefPubMedGoogle Scholar
  • 35 Waki H, Yamauchi T, Kamon J et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278: 40352-40363
    CrossrefPubMedGoogle Scholar
  • 36 Xu A, Wang Y, Lam KS et al. Vascular actions of adipokines molecular mechanisms and therapeutic implications. Adv Pharmacol 2010; 60: 229-255
    PubMedGoogle Scholar