Interleukin-15 treatment improves glucose homeostasis and insulin sensitivity in obese mice

被引:58
作者
Barra, N. G. [1 ,2 ]
Chew, M. V. [1 ,2 ]
Holloway, A. C. [3 ]
Ashkar, A. A. [1 ,2 ]
机构
[1] McMaster Univ, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada
[2] McMaster Univ, Inst Infect Dis Res, Hamilton, ON L8S 4K1, Canada
[3] McMaster Univ, Dept Obstet & Gynecol, Hamilton, ON L8S 4K1, Canada
基金
加拿大健康研究院;
关键词
antiobesity drug; diabetes complications; experimental pharmacology; glucose metabolism; insulin resistance; ADIPOSE-TISSUE; RESISTANCE; ISLETS; IL-15; CELLS;
D O I
10.1111/j.1463-1326.2011.01495.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The prevalence of metabolic diseases associated with obesity, such as type 2 diabetes, continues to rise along with obesity rates. Recently, obesity has been described as an inflammatory condition, suggesting a link between the dysregulation in proinflammatory cytokine production and the aetiology of these metabolic diseases. While known as an immunomodulatory cytokine, Interleukin-15 (IL-15) has been shown to have effects on adipose tissue and induce weight loss in diet-induced obese mice. As weight loss improves glucose homeostasis, the goal of this study was to determine whether IL-15 impacts glucose regulation in a mouse model of diet-induced obesity. Our data demonstrate that IL-15 treatment significantly improves insulin sensitivity and glucose and insulin responses to an oral glucose challenge compared to obese counterparts and/or lean controls. These results show that IL-15 may be a novel therapeutic target for the treatment of obesity and its associated abnormal glucose regulation.
引用
收藏
页码:190 / 193
页数:4
相关论文
共 12 条
[1]   Interleukin-15 Contributes to the Regulation of Murine Adipose Tissue and Human Adipocytes [J].
Barra, Nicole G. ;
Reid, Sarah ;
MacKenzie, Randy ;
Werstuck, Geoff ;
Trigatti, Bernardo L. ;
Richards, Carl ;
Holloway, Alison C. ;
Ashkar, Ali A. .
OBESITY, 2010, 18 (08) :1601-1607
[2]   Interleukin-15 increases glucose uptake in skeletal muscle -: An antidiabetogenic effect of the cytokine [J].
Busquets, Silvia ;
Figueras, Maite ;
Almendro, Vanessa ;
Lopez-Soriano, Francisco J. ;
Argiles, Josep M. .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2006, 1760 (11) :1613-1617
[3]   IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice [J].
Cardozo, AK ;
Proost, P ;
Gysemans, C ;
Chen, MC ;
Mathieu, C ;
Eizirik, DL .
DIABETOLOGIA, 2003, 46 (02) :255-266
[4]   IL-15 has innate anti-tumor activity independent of NK and CD8 T cells [J].
Davies, Elizabeth ;
Reid, Sarah ;
Medina, Maria Fe ;
Lichty, Brian ;
Ashkar, Ali A. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2010, 88 (03) :529-536
[5]   An Integrated Approach to Diabetic Retinopathy Research [J].
Gardner, Thomas W. ;
Abcouwer, Steven F. ;
Barber, Alistair J. ;
Jackson, Gregory R. .
ARCHIVES OF OPHTHALMOLOGY, 2011, 129 (02) :230-235
[6]   Adipose tissue dysfunction in obesity, diabetes, and vascular diseases [J].
Hajer, Gideon R. ;
van Haeften, Timon W. ;
Visseren, Frank L. J. .
EUROPEAN HEART JOURNAL, 2008, 29 (24) :2959-2971
[7]   The role of interleukin-6 in insulin resistance, body fat distribution and energy balance [J].
Hoene, M. ;
Weigert, C. .
OBESITY REVIEWS, 2008, 9 (01) :20-29
[8]   Effect of combining rosiglitazone with either metformin or insulin on β-cell mass and function in an animal model of Type 2 diabetes characterized by reduced β-cell mass at birth [J].
Holloway, Alison C. ;
Hettinga, Bart P. ;
Gerstein, Hertzel C. .
JOURNAL OF DIABETES, 2011, 3 (01) :74-81
[9]   Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance [J].
Netea, MG ;
Joosten, LAB ;
Lewis, E ;
Jensen, DR ;
Voshol, PJ ;
Kullberg, BJ ;
Tack, CJ ;
van Krieken, H ;
Kim, SH ;
Stalenhoef, AF ;
Van de Loo, FA ;
Verschueren, I ;
Pulawa, L ;
Akira, S ;
Eckel, RH ;
Dinarello, CA ;
Van den Berg, W ;
Van der Meer, JWM .
NATURE MEDICINE, 2006, 12 (06) :650-656
[10]   Association between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass [J].
Nielsen, Anders Rinnov ;
Hojman, Pernille ;
Erikstrup, Christian ;
Fischer, Christian Philip ;
Plomgaard, Peter ;
Mounier, Remi ;
Mortensen, Ole Hartvig ;
Broholm, Christa ;
Taudorf, Sarah ;
Krogh-Madsen, Rikke ;
Lindegaard, Birgitte ;
Petersen, Anne Marie Winther ;
Gehl, Julie ;
Pedersen, Bente Klarlund .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (11) :4486-4493