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Exp Clin Endocrinol Diabetes 2011; 119(3): 177-181
DOI: 10.1055/s-0030-1261965
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Substance P is Associated with the Development of Obesity, Chronic Inflammation and Type 2 Diabetes Mellitus

J. Fu1 , B. Liu2 , P. Liu3 , L. Liu7 , G. Li3 , B. Wu5 , X. Liu6
  • 1Health Screen Center of The First Affiliated Hospital of Harbin Medical University, Harbin, China
  • 2Cardiology Department of The First Affiliated Hospital of Harbin Medical University, Harbin, China
  • 3Immunology Department of Harbin Medical University, Harbin, China
  • 4Harbin Medical University, Harbin, China
  • 5Heilongjiang University of Chinese Medicine, Harbin, China
  • 6Endocrinology Department of The First Affiliated Hospital of Harbin Medical University, Harbin, China
  • 7Shiga University of Medical Science, Otsu, Japan
Further Information

Publication History

received 05.05.2010 first decision 30.06.2010

accepted 30.06.2010

Publication Date:
23 July 2010 (online)

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Abstract

Background: Substance P (SP) is an important neurotransmitter and is an important pathogenic factor in obesity. However, the relationships between the inflammatory cytokines interleukin-6 (IL-6), C reactive protein (CRP) and SP with obesity and type 2 diabetes mellitus (T2DM) are poorly understood.

Objective: We investigated the associations between SP, IL-6 and CRP with obesity and T2DM.

Subjects and Methods: The subjects comprised patients who underwent physical examinations at the First Affiliated Hospital of Harbin Medical University between January 2006 and December 2008. Overall, 156 subjects participated in this study, including 63 obese (BMI >25 kg/m2) subjects with T2DM, and 58 obese and 35 lean subjects without T2DM. Patient characteristics were collected from a health questionnaire form. Anthropometric measurements and fasting blood samples were assessed. SP, CRP, IL-6 and HOMA-IR were converted into log values.

Results: SP, IL-6, CRP and HOMA-IR were significantly higher (P<0.05) in obese T2DM subjects compared with obese and lean subjects without T2DM. All 3 parameters were significantly associated with other risk factors for diabetes, including BMI, blood pressure, plasma glucose and high-density lipoprotein levels. After adjusting for age, SP was significantly and positively correlated with BMI and logHOMA-IR (P≤0.05); correlation coefficients were higher in obese T2DM subjects than in lean or obese subjects without T2DM.

Conclusions: High levels of SP and IL-6 were significantly associated with obesity and risk factors for T2DM. Associations were of greatest in obese T2DM subjects. Obesity and T2DM show additive effects on the association between SP and BMI or logHOMA-IR.

Key words

C-reactive protein - diabetes - HOMA-IR - interleukin-6 - obesity - substance P

References

  • 1 Alvaro G, Di Fabio R. Neurokinin 1 receptor antagonists – current prospects.  Curr Opin Drug Discov Devel. 2007;  10 (5) 613-621
    Google Scholar
  • 2 American Diabetes Association. . Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. 1997;  20 (7) 1183-1197
    Google Scholar
  • 3 Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars.  Science. 2005;  307 (5717) 1909-1914
    Google Scholar
  • 4 Burdo JR, Chen Q, Calcutt NA. et al . The pathological interaction between diabetes and presymptomatic Alzheimer's disease.  Neurobiol Aging. 2009;  30 (12) 1910-1917
    Google Scholar
  • 5 Chang MN, Leeman SE. Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as Substance P.  J Biol Chem. 1970;  245 (18) 4784-4790
    Google Scholar
  • 6 Cummings J, MacLellan A, Langdon SP. et al . Stability and in vitro metabolism of the mitogenic neuropeptide antagonists [D-Arg1,D-Phe5, D-Trp7,9, Leu11]-substance P and [Arg6, D-Trp7,9, MePhe8]-substance P (6-11) characterized by high-performance liquid chromatography.  J Pharm Biomed Anal. 1994;  12 (6) 811-819
    Google Scholar
  • 7 de Almeida BB, Mathias MG, Portari GV. et al . Chronic acetonemia alters liver oxidative balance and lipid content in rats. A model of NASH?.  Exp Clin Endocrinol Diabetes. 2010;  118 (1) 61-63
    Google Scholar
  • 8 Dietrich MO, Horvath TL. Feeding signals and brain circuitry.  Eur J Neurosci. 2009;  30 (9) 1688-1696
    Google Scholar
  • 9 Fleischman A, Shoelson SE, Bernier R. et al . Salsalate improves glycemia and inflammatory parameters in obese young adults.  Diabetes Care. 2008;  31 (2) 289-294
    Google Scholar
  • 10 Gustafson B. Adipose Tissue, Inflammation and Atherosclerosis.  J Atheroscler Thromb. 2010 Feb 3;  [Epub ahead of print]
    Google Scholar
  • 11 Harrison S, Geppetti P. Substance P.  Int J Biochem Cell Biol. 2001;  33 (6) 555-576
    Google Scholar
  • 12 International Diabetes Federation – Western Pacific Region. .Asian-Pacific Type 2 diabetes Policy Group. Type 2 Diabetes: Practical Targets and Treatments, 4th Edition 2005 Available at: http://www.idf.org/webdata/docs/T2D_practical_tt.pdf (Last accessed: April 13, 2010)
  • 13 Karagiannides I, Kokkotou E, Tansky M. et al . Induction of colitis causes inflammatory responses in fat depots: evidence for substance P pathways in human mesenteric preadipocytes.  Proc Natl Acad Sci U S A. 2006;  103 (13) 5207-5212
    Google Scholar
  • 14 Karagiannides I, Torres D, Tseng YH. et al . Substance P as a novel anti-obesity target.  Gastroenterology. 2008;  134 (3) 747-755
    Google Scholar
  • 15 Koon HW, Zhao D, Zhan Y. et al . Substance P mediates antiapoptotic responses in human colonocytes by Akt activation.  Proc Natl Acad Sci U S A. 2007;  104 (6) 2013-2018
    Google Scholar
  • 16 Joslin G, Krause JE, Hershey AD. et al . Amyloid-beta peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor.  J Biol Chem. 1991;  266 (32) 21897-21902
    Google Scholar
  • 17 Mather KJ, Funahashi T, Matsuzawa Y. et al . Diabetes Prevention Program. Adiponectin, change in adiponectin, and progression to diabetes in the Diabetes Prevention Program.  Diabetes. 2008;  57 (4) 980-986
    Google Scholar
  • 18 Miklossy J, Qing H, Radenovic A. et al . Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes.  Neurobiol Aging. 2008. Oct 23;  [Epub ahead of print]
    Google Scholar
  • 19 Percik R, Stumvoll M. Obesity and cancer.  Exp Clin Endocrinol Diabetes. 2009;  117 (10) 563-566
    Google Scholar
  • 20 Pieri M, Amadoro G, Carunchio I. et al . SP protects cerebellar granule cells against beta-amyloid-induced apoptosis by down-regulation and reduced activity of Kv4 potassium channels.  Neuropharmacology. 2010;  58 (1) 268-276
    Google Scholar
  • 21 Quartara L, Maggi CA. The tachykinin NK1 receptor. Part I: ligands and mechanisms of cellular activation.  Neuropeptides. 1997;  31 (6) 537-563
    Google Scholar
  • 22 Ribeiro-da-Silva A, Hokfelt T. Neuroanatomical localisation of Substance P in the CNS and sensory neurons.  Neuropeptides. 2000;  34 (5) 256-271
    Google Scholar
  • 23 Samy N, Hashim M, Sayed M. et al . Clinical significance of inflammatory markers in polycystic ovary syndrome: their relationship to insulin resistance and body mass index.  Dis Markers. 2009;  26 (4) 163-170
    Google Scholar
  • 24 Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030.  Diabetes Res Clin Pract. 2010;  87 (1) 4-14
    Google Scholar
  • 25 Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance.  Gastroenterology. 2007;  132 (6) 2169-2180
    Google Scholar
  • 26 Takenouchi T, Munekata E. Trophic effects of substance P and beta-amyloid peptide on dibutyryl cyclic AMP-differentiated human leukemic (HL-60) cells.  Life Sci. 1995;  56 (26) PL479-PL484
    Google Scholar
  • 27 Thorand B, Kolb H, Baumert J. et al . Elevated levels of interleukin-18 predict the development of type 2 diabetes: results from the MONICA/KORA Augsburg Study, 1984–2002.  Diabetes. 2005;  54 (10) 2932-2938
    Google Scholar
  • 28 Tian F, Luo R, Zhao Z. et al . Blockade of the RAS increases plasma adiponectin in subjects with metabolic syndrome and enhances differentiation and adiponectin expression of human preadipocytes.  Exp Clin Endocrinol Diabetes. 2010;  118 (4) 258-265
    Google Scholar
  • 29 Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease.  Lancet. 2005;  365 (9473) 1817-1820
    Google Scholar
  • 30 World Health Organization. . Obesity and overweight.  2003;  Available at: http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/ (Last accessed: April 12, 2010)
    Google Scholar
  • 31 World Health Organization – Western Pacific Region . The Asia-Pacific perspective: Redefining obesity and its treatment.  2000;  Available at: http://www.wpro.who.int/internet/resources.ashx/NUT/Redefining+obesity.pdf (Last accessed: April 26, 2010)
    Google Scholar

Correspondence

X. LiuMD, MSc 

Endocrinology Department

The First Affiliated Hospital of Harbin Medical University

Harbin

China

Phone: +86/451/8555 5813

Fax: +86/451/5364 1798

Email: liuxiaomin57@yahoo.com.cn

Email: fujunyk@hotmail.com

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