Research Article
Relationship of Soluble RAGE with Insulin Resistance and Beta
Cell Function during Development of Type 2 Diabetes Mellitus
Subrata Kumar Biswas,
1
Sabreena Mohtarin,
1
Sonchita Rani Mudi,
2
Taznuva Anwar,
1
Laila Anjuman Banu,
3
Sheikh Md. Khorshed Alam,
1
Md. Fariduddin,
4
and M. Iqbal Arslan
1
1
Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka 1000, Bangladesh
2
Department of Biochemistry and Cell Biology, Bangladesh Institute of Research and Rehabilitation in Diabetes,
Endocrine and Metabolic Disorders (BIRDEM), 122 Kazi Nazrul Islam Avenue, Shahbag, Dhaka 1000, Bangladesh
3
Department of Anatomy, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka 1000, Bangladesh
4
Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka 1000, Bangladesh
Correspondence should be addressed to Subrata Kumar Biswas; su.biswas@yahoo.com
Received 14 April 2015; Accepted 12 May 2015
Academic Editor: Roberto Mallone
Copyright © 2015 Subrata Kumar Biswas et al. his is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
his study examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) alter in prediabetes
and correlate with insulin resistance (IR) and beta cell function in prediabetes and newly diagnosed type 2 diabetes mellitus
(T2DM). Subjects without previous history of diabetes were recruited and grouped as control, prediabetes, and newly diagnosed
T2DM. he control subjects ( = 40) and people with prediabetes ( = 52) and diabetes ( = 66) were similar in terms of age,
sex, BMI, systolic and diastolic BP, and fasting insulin level. HOMA-IR was found signiicantly higher in people with diabetes than
control subjects ( < 0.001) and people with prediabetes ( = 0.005); and HOMA-%B was found signiicantly deteriorated in
people with diabetes ( < 0.001) compared to control subjects and people with prediabetes. However, serum sRAGE levels did
not show any signiicant alteration in people with prediabetes compared to control subjects. Moreover, univariate and multivariate
analyses did not identify any signiicant correlation and statistical association of sRAGE with HOMA-IR and HOMA-%B in people
with prediabetes and newly diagnosed T2DM. Our data suggest that serum sRAGE levels do not alter in people with prediabetes
compared to control subjects and do not correlate or associate with IR and beta cell function during development of T2DM.
1. Introduction
he receptor for advanced glycation end products (RAGE)
is a cell surface receptor of immunoglobulin superfamily.
RAGE activation through ligand binding can induce chronic
inlammation and oxidative stress, and it has been linked
with diseases like diabetic complications, cardiovascular and
neurodegenerative diseases, and cancer [1]. A soluble form
of RAGE (sRAGE), which is a splice variant of full-length
RAGE or a shedding/cleavage product of membrane-bound
RAGE, has been found circulating in the plasma [2, 3]. he
sRAGE can bind and sequester RAGE ligands and thereby can
reduce RAGE activation. herefore, the sRAGE is generally
considered as protective against diseases originating from
RAGE activation [1–3].
RAGE-ligand interaction was previously claimed to be
involved in the pathogenesis of autoimmune diabetes, and
treatment with sRAGE was shown to efectively prevent
transfer of diabetes into NOD/scid mice that receive spleen
cells from a diabetic NOD donor [4]. Subsequently, blockade
of high-mobility group box 1, a RAGE ligand, was shown
to inhibit insulitis progression and diabetes development in
NOD mice [5]. A minor role of genetic variation in RAGE
was also suggested to be associated with insulin resistance
(IR) in a human population [6]. However, recent studies
have suggested that low levels of circulating sRAGE may be
involved in the development of diabetes mellitus [7–9]. A
declining level of sRAGE at the time of seroconversion to
autoantibody positivity has been suspected to be a predictor
of type 1 diabetes [7, 8], and an independent association has
Hindawi Publishing Corporation
Journal of Diabetes Research
Volume 2015, Article ID 150325, 6 pages
http://dx.doi.org/10.1155/2015/150325