The Open Public Health Journal


ISSN: 1874-9445 ― Volume 10, 2017
RESEARCH ARTICLE

Relation of Plasma Obestatin Levels with BMI and HOMA-IR in Syrian Obese Patients with Type 2 Diabetes



Hiba Alhalbouni1, *, Youns Kabalan2, Faizeh Alquobaili1
1 Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, Syria
2 Department of Endocrinology, Faculty of Medicine, Damascus University, Damascus, Syria

Abstract

Background:

Obestatin is a novel hormone derived from preproghrelin, which was reported to inhibit appetite and gastric motility.

Study Aim:

This study aimed to investigate plasma obestatin levels in obese patients with T2D patients, which had not been studied clearly in last researches.

Methods:

23 normal weight subjects, 35 obese subjects and 31 obese patients with T2D participated in the study, the body mass index was calculated. Fasting glucose and insulin levels were measured and the homeostasis model assessment of insulin resistance (HOMA-IR) was determined. Plasma obestatin levels were measured with enzyme-linked immune sorbent assay (ELISA). The relationship between plasma obestatin levels and biochemical parameters was also analyzed.

Results:

Fasting obestatin was significantly lower in obese patients with T2D, comparing to control subjects (mean=6.35 vs12.38ng/ml) and to the non-patients obese group (mean=6.35 vs 7.76 ng/ml). Obestatin levels correlated significantly and negatively with BMI (R=-0. 451; P=0. 01), basal insulin levels (R=-0.737, P<0.0001) and HOMA-IR (R=-0. 764, P<0.0001) in diabetic patients.

Conclusion:

Our results suggest that obestatin may contribute to body weight regulation, and insulin sensitivity could be affected by obestatin levels.

Keywords: Obestatin, BMI, HOMA-IR, Type 2 diabetes mellitus, Homeostasis, Insulin.


Article Information


Identifiers and Pagination:

Year: 2017
Volume: 10
First Page: 132
Last Page: 139
Publisher Id: TOPHJ-10-132
DOI: 10.2174/1874944501710010132

Article History:

Received Date: 16/04/2017
Revision Received Date: 02/06/2017
Acceptance Date: 29/06/2017
Electronic publication date: 31/08/2017
Collection year: 2017

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© 2017 Alhalbouni et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, Syria, Tel: +963937276440; E-mail: Dr.hiba.alhalbouni@hotmail.com




1. INTRODUCTION

Diabetes is a major health problem which its prevalence has been increasing over the last years [1 World Health Organization. Global report on diabetes. World Health Organization; 2016.], Type 2 diabetes (T2D) accounts for 90-95% of diabetes cases, and characterized by insulin resistance, and obesity in most patients [2Fowler MJ. Classification of diabetes: Not all hyperglycemia is the same. Clin Diabetes 2007; 25(2): 74-6.
[http://dx.doi.org/10.2337/diaclin.25.2.74]
], and obesity in most patients [3 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37(Suppl. 1): 81-90.
[http://dx.doi.org/10.2337/dc14-S081] [PMID: 23959568]
], and the aim of the medical treatment is to decrease insulin resistance and increase beta cell insulin production [4Fowler MJ. Diagnosis, classification, and lifestyle treatment of diabetes. Clin Diabetes 2010; 28(2): 79-86.
[http://dx.doi.org/10.2337/diaclin.28.2.79]
].

By using bioinformatics, Zhang et al. (2005) identified a 23-amino- acid amidated peptide called obestatin, encoded by the same precursor gene of ghrelin [5Zhang JV, Ren P-G, Avsian-Kretchmer O, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 2005; 310(5750): 996-9.
[http://dx.doi.org/10.1126/science.1117255] [PMID: 16284174]
]. Obestatin was claimed to act as a physiological opponent of ghrelin, inhibiting ghrelin orexigenic action. Therefore whereas ghrelin effects are mainly diabetogenic, obestatin behaves as antidiabetogenic peptide by positively affecting on lipid and glucose metabolism [6Trovato L, Gallo D, Settanni F, Gesmundo I, Ghigo E, Granata R. Is it really doing something? How Gut Brain Control Metab 2014; 42: 175-85.]. Obestatin and ghrelin are largely produced throughout the GI tract (like stomach, pancreas and duodenum) with predominant expression in the gastric mucosa [7Zhao CM, Furnes MW, Stenström B, Kulseng B, Chen D. Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: An immunohistochemical and electron-microscopic study. Cell Tissue Res 2008; 331(3): 575-87.
[http://dx.doi.org/10.1007/s00441-007-0514-3] [PMID: 18071756]
]. In rats, obestatin is found in the GI tract, within the A-like cells and oxyntic glands of the gastric mucosa. In humans, the majority of obestatin specifically found in the crypts of Lieberkuhn and Brunner’s glands, and absence from the colon [8Grönberg M, Tsolakis AV, Magnusson L, Janson ET, Saras J. Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands. J Histochem Cytochem 2008; 56(9): 793-801.
[http://dx.doi.org/10.1369/jhc.2008.951145] [PMID: 18474938]
].

Obestatin expression has been demonstrated in other tissues, including pancreas, adipose tissue, testis, liver, lung, thyroid, mammary gland, and skeletal muscle, suggesting autocrine/paracrine effects [9Gesmundo I, Gallo D, Favaro E, Ghigo E, Granata R. Obestatin: A new metabolic player in the pancreas and white adipose tissue. IUBMB Life 2013; 65(12): 976-82.
[http://dx.doi.org/10.1002/iub.1226] [PMID: 24217898]
].

Several groups have demonstrated obestatin secretion from rat WAT and adipocytes from both mice and humans [10Gurriarán-Rodríguez U, Al-Massadi O, Roca-Rivada A, et al. Obestatin as a regulator of adipocyte metabolism and adipogenesis. J Cell Mol Med 2011; 15(9): 1927-40.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01192.x] [PMID: 21029370]
, 11Granata R, Gallo D, Luque RM, et al. Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation. The FASEB Journal 2012; 26: 3393-411.].

In 2008, obestatin was reported to be secreted by human pancreatic islets and pancreatic beta cell lines, to enhance their viability in response to both serum starvation and cytokines and to inhibit apoptosis [12Granata R, Settanni F, Gallo D, et al. Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function. Diabetes 2008; 57(4): 967-79.
[http://dx.doi.org/10.2337/db07-1104] [PMID: 18162507]
, 13Favaro E, Granata R, Miceli I, et al. The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways. Diabetologia 2012; 55(4): 1058-70.
[http://dx.doi.org/10.1007/s00125-011-2423-y] [PMID: 22231124]
].

Obestatin promotes the generation of pancreatic islet-like clusters together with increased insulin gene expression during endocrine pancreatic precursor cell selection and differentiation. This seems to happen via pathways including fibroblast growth factor receptors, neurogenin 3 and Notch receptors, which suggest its role in development and regeneration of pancreas [14Baragli I, Grande C, Gesmundo I, et al. Obestatin enhances in vitro generation of pancreatic islets through regulation of developmental pathways. PLoS One 2013; 8(5): e64374.
[http://dx.doi.org/10.1371/journal.pone.0064374] [PMID: 23741322]
]. Notably, the reported anti-apoptotic effects of obestatin in the pancreas seem to mediate via support of islet vascularization [13Favaro E, Granata R, Miceli I, et al. The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways. Diabetologia 2012; 55(4): 1058-70.
[http://dx.doi.org/10.1007/s00125-011-2423-y] [PMID: 22231124]
].

A lot of studies show that obestatin suppress food intake, body weight gain, and jejuna constriction in experiment animals [5Zhang JV, Ren P-G, Avsian-Kretchmer O, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 2005; 310(5750): 996-9.
[http://dx.doi.org/10.1126/science.1117255] [PMID: 16284174]
], which indicates that obestatin may contribute to the regulation of body weight.

Many researchers have studied obestatin in obese people generally but not in obese diabetes patients, except one study (Lipple et al. 2008 [15Lippl F, Erdmann J, Lichter N, et al. Relation of plasma obestatin levels to bmi, gender, age and insulin. Horm Metab Res 2008; 40(11): 806-12.
[http://dx.doi.org/10.1055/s-2008-1081503] [PMID: 18622896]
]). This motivated us to study obestatin levels in obese patients with type 2 diabetes, and investigate the relationship of obestatin levels with insulin resistance and body weight regulation in those patients.

2. MATERIALS AND METHODS

Our study is a prospective cross-sectional study. It was conducted at the endocrine clinic at Al-Moassah University Hospital and Faculty of Pharmacy, Damascus University, Damascus, Syria. Informed consent was given to all participants. Ethical approval obtained from the ethical committee of Damascus University. The study included 89 participants divided into three groups:

Normal weight subjects as Control (23 subjects: 9 males, 14 females), obese patients with T2D (31 subjects:10 males, 21 females), obese subjects (35 subjects: 7 males, 28 females).

The obese patients were admitted for the treatment of obesity and type 2 diabetes, they were not consuming alcohol nor tobacco smoking, and they had not been practicing of physical activity.

Based on the World Health Organization (WHO) body weight classes, subjects were normal weight when BMI ranges from 18.5 to 24.9 kg/m2, Overweight when BMI ranges from 25 to 29.9 kg/m2, obese when BMI≥ 30 kg/m2 [16WHO (World Health Organization). WHO Global Database on Body Mass Index 2016.].

Both control and obese subjects have no family history of T2DM or other diseases.T2D was diagnosed using the FBG (Fasting Blood Glucose) and OGTT (Oral Glucose Tolerance Test) were used [17American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care 2016; 39(Suppl. 1): S13-22.
[PMID: 26696675]
].

Patients with diabetes complications and those with type 1 diabetes, congestive heart failure, or any major diseases were eliminated. All subjects were of Syrian origin.

Basal blood samples were drawn between 9-10 A.M. after a 12-hour overnight fast. Samples were collected into both EDTA plastic tubes to analyze obestatin in plasma and HbA1c and empty tubes to do other biochemical analysis, then centrifuged at 4000 rpm (1789×g) for 5 minutes at 4ºC to isolate plasma and serum. Biochemical analysis of glucose and HbA1c were performed at Children's Hospital of Damascus within two hours of sampling. Obestatin levels were measured by sandwich ELISA method using a commercial kit (Sun Red, China) and spectro photo microplate reader at Damascus University (Elysisuno - Human, Germany). Glucose was measured by the enzymatic colorimetric method using an automatic analyzer (Hitachi 911, Japan) and commercial assay kits (Audit Diagnostics, Ireland). Insulin levels were measured by ELISA method using a commercial kit (NOVA TEC Immundiagnostica GmbH, Germany).

Statistical analysis was performed using SPSS 20.0 (IBM Inc., USA). All data were expressed as mean ± SD. Data was analyzed using T –Student to compare the results between groups. categorical variables were compared by using chi-square test. Pearson correlation was used to study the correlation between studied parameters. p<0.05 was considered significant.

3. RESULTS

The results of studied biochemical parameters were shown in (Table 1).

Table 1
Demographic characteristics and biochemical parameters of the study population.


Obestatin levels did not significantly differ from men and women.

Mean ± SD values of obestatin were: 12.38 ± 3.74 ng/ml for control subjects, 7.76 ± 2.09ng/ml for obese subjects. obestatin levels were significantly lower (p<0.0001) in obese subjects compared to control subjects.

Mean ± SD values of obestatin were: 6.35 ± 2.48 ng/ml for patients with T2D. Obestatin levels were significantly lower (p<0.0001) in patients with T2D compared to control subjects.

Obestatin levels were significantly lower in patients with T2D as compared to obese subjects (p = 0.014) (Fig. 1).

Fig. (1)
Plasma obestatin levels in the three groups.


Levels of HOMA-IR (Fig. 2) and fasting blood glucose (Fig. 3) were significantly higher (P<0.0001) in diabetic patients as compared to control group and obese subjects, whereas levels of insulin were not significantly (p = 0.817) higher in patients with T2D compared to obese subjects (Fig. 4).

Fig. (2)
HOMA-IR in the three groups.


Fig. (3)
Glucose levels in the three groups.


Fig. (4)
Insulin levels in the three groups.


Fig. (5)
Correlation between obestatin and BMI, insulin, glucose, HOMA-IR and age.


Levels of obestatin correlated significantly and inversely with BMI values (R = -0. 451; P = 0.01), insulin levels (R = -0. 737, P<0. 0001) and HOMA-IR (R = -0. 764,P<0.0001), but it did not correlate significantly with fasting blood glucose levels (R =- 0. 165, P = 0. 375) nor age (R = -0. 204, P = 0.271) in diabetic patients (Fig. 5).

4. DISCUSSION

In this study, we measured plasma obestatin levels in patients with type 2 diabetes (T2D) to better understand the role of Obestatin in this disease. Our results showed that Obestatin levels were significantly lower in patients with T2D as compared to control group (P=0.014).

These findings were in agreement with the Lipple et al., 2008 in Germany, who found lower obestatin levels in obese patient with type 2 diabetes compared to control subjects [15Lippl F, Erdmann J, Lichter N, et al. Relation of plasma obestatin levels to bmi, gender, age and insulin. Horm Metab Res 2008; 40(11): 806-12.
[http://dx.doi.org/10.1055/s-2008-1081503] [PMID: 18622896]
], but the variations did not reach the level of statistical significance, and obestatin levels differed according to gender. This difference might be due to variations in environment and the type of food.

A study by Lu et al. 2016, who had reported a very similar study found higher obestatin levels in obese patient with type 2 diabetes as compared to controls [18Lu L, Chen L, Zheng L, Liu D, Zhou D, Chen Z. Changes of circulating ghrelin and obestatin levels in obese patients with or without type 2 diabetes mellitus. Int J Clin Exp Med 2016; 9(8): 16425-31.]; this difference might be due to the relatively small number of participants in their study (n:27), and diurnal variations in obestatin production, which had been reported to follow a pulsatile pattern [19Zizzari P, Longchamps R, Epelbaum J, Bluet-Pajot MT. Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents. Endocrinology 2007; 148(4): 1648-53.
[http://dx.doi.org/10.1210/en.2006-1231] [PMID: 17204551]
].

Obestatin levels in our study correlated inversely and significantly with BMI, insulin, and HOMA- IR values in obese patients with T2D (Fig. 5). These results suggested that obestatin concentrations could affect insulin resistance and body weight.

However, these findings were in agreement with a previous study(Qi et al. 2007), which found that obestatin levels correlated inversely and significantly with BMI (P = 0.035), insulin (P = 0.003) and HOMA-IR (P = 0.031) values, and did not correlate significantly with age (P = 0.162) nor glucose (P = 0.162) in diabetic patients (but their patients were not obese) [20Qi X, Li L, Yang G, et al. Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007; 66(4): 593-7.
[PMID: 17371480]
]

A study by Ma et al. 2014 found that plasma obestatin concentrations in diabetic patients were significantly lower than those in normal glucose tolerance subjects. This is consistent with our results, although, all their subjects were middle-aged (41-64 years) and old (65-76 years) and they were not obese, and they showed that plasma ghrelin was negatively associated with fasting glucose and Urine Albumin-to-Creatinine Ratio (UACR), so that the lower ghrelin levels might be a potential indicator for renal dysfunction in patients with T2D [21Ma X, Zhao Y, Wang Q, et al. Plasma ghrelin concentrations are negatively correlated with urine albumin-to-creatinine ratio in newly diagnosed type 2 diabetes. Am J Med Sci 2014; 348(5): 382-6.
[http://dx.doi.org/10.1097/MAJ.0000000000000297] [PMID: 24875659]
].

Another study by Taskin et al. 2015 showed that levels of obestatin were significantly lower in obese group than non-obese and control groups (p < 0.001). However, subjects were patients with polycystic ovary syndrome PCOS, and serum copeptin levels were significantly higher in obese PCOS group than they were in non-obese PCOS and control groups (p < 0.001) [22Taskin MI, Bulbul E, Adali E, Hismiogulları AA, Inceboz U. Circulating levels of obestatin and copeptin in obese and nonobese women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2015; 189: 19-23.
[http://dx.doi.org/10.1016/j.ejogrb.2015.03.006] [PMID: 25837320]
].

A study by Huang et al. 2014 showed that in the evolution of type 2 diabetes, the increase of visceral fat area could be the initiating factor, leading elevated acyl ghrelin(bioactive form), reduced unacyl ghrelin, insulin resistance, and finally elevated blood glucose [23Huang L, Tong Y, Zhang F, et al. Increased acyl ghrelin but decreased total ghrelin and unacyl ghrelin in Chinese Han people with impaired fasting glucose combined with impaired glucose tolerance. Peptides 2014; 60: 86-94.
[http://dx.doi.org/10.1016/j.peptides.2014.07.022] [PMID: 25102450]
].

CONCLUSION

Our results suggest that obestatin levels may contribute in body weight regulation and insulin resistance in patients with type 2 diabetes.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This research have been agreed by the ethical committee on human experimentation in the faculty of Pharmacy- Damascus University,which followed the ethical standards of the responsible committee on human experimentation.

HUMAN AND ANIMAL RIGHTS

No animals were used in this research. All research procedures followed were in accordance with the ethical standards of the committee responsible for human experimentation (institutional and national), and with the Helsinki Declaration of 1975, as revised in 2008 (http://www.wma.net/en/20activities/10ethics/10helsinki/)

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

We would like to thank the staff at Al-Assad University Hospital and biochemistry laboratory in Children's Hospital of Damascus for performing the biochemical tests as soon as possible.

REFERENCES

[1] World Health Organization. Global report on diabetes. World Health Organization; 2016.
[2] Fowler MJ. Classification of diabetes: Not all hyperglycemia is the same. Clin Diabetes 2007; 25(2): 74-6.
[http://dx.doi.org/10.2337/diaclin.25.2.74]
[3] American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37(Suppl. 1): 81-90.
[http://dx.doi.org/10.2337/dc14-S081] [PMID: 23959568]
[4] Fowler MJ. Diagnosis, classification, and lifestyle treatment of diabetes. Clin Diabetes 2010; 28(2): 79-86.
[http://dx.doi.org/10.2337/diaclin.28.2.79]
[5] Zhang JV, Ren P-G, Avsian-Kretchmer O, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 2005; 310(5750): 996-9.
[http://dx.doi.org/10.1126/science.1117255] [PMID: 16284174]
[6] Trovato L, Gallo D, Settanni F, Gesmundo I, Ghigo E, Granata R. Is it really doing something? How Gut Brain Control Metab 2014; 42: 175-85.
[7] Zhao CM, Furnes MW, Stenström B, Kulseng B, Chen D. Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: An immunohistochemical and electron-microscopic study. Cell Tissue Res 2008; 331(3): 575-87.
[http://dx.doi.org/10.1007/s00441-007-0514-3] [PMID: 18071756]
[8] Grönberg M, Tsolakis AV, Magnusson L, Janson ET, Saras J. Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands. J Histochem Cytochem 2008; 56(9): 793-801.
[http://dx.doi.org/10.1369/jhc.2008.951145] [PMID: 18474938]
[9] Gesmundo I, Gallo D, Favaro E, Ghigo E, Granata R. Obestatin: A new metabolic player in the pancreas and white adipose tissue. IUBMB Life 2013; 65(12): 976-82.
[http://dx.doi.org/10.1002/iub.1226] [PMID: 24217898]
[10] Gurriarán-Rodríguez U, Al-Massadi O, Roca-Rivada A, et al. Obestatin as a regulator of adipocyte metabolism and adipogenesis. J Cell Mol Med 2011; 15(9): 1927-40.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01192.x] [PMID: 21029370]
[11] Granata R, Gallo D, Luque RM, et al. Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation. The FASEB Journal 2012; 26: 3393-411.
[12] Granata R, Settanni F, Gallo D, et al. Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function. Diabetes 2008; 57(4): 967-79.
[http://dx.doi.org/10.2337/db07-1104] [PMID: 18162507]
[13] Favaro E, Granata R, Miceli I, et al. The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways. Diabetologia 2012; 55(4): 1058-70.
[http://dx.doi.org/10.1007/s00125-011-2423-y] [PMID: 22231124]
[14] Baragli I, Grande C, Gesmundo I, et al. Obestatin enhances in vitro generation of pancreatic islets through regulation of developmental pathways. PLoS One 2013; 8(5): e64374.
[http://dx.doi.org/10.1371/journal.pone.0064374] [PMID: 23741322]
[15] Lippl F, Erdmann J, Lichter N, et al. Relation of plasma obestatin levels to bmi, gender, age and insulin. Horm Metab Res 2008; 40(11): 806-12.
[http://dx.doi.org/10.1055/s-2008-1081503] [PMID: 18622896]
[16] WHO (World Health Organization). WHO Global Database on Body Mass Index 2016.
[17] American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care 2016; 39(Suppl. 1): S13-22.
[PMID: 26696675]
[18] Lu L, Chen L, Zheng L, Liu D, Zhou D, Chen Z. Changes of circulating ghrelin and obestatin levels in obese patients with or without type 2 diabetes mellitus. Int J Clin Exp Med 2016; 9(8): 16425-31.
[19] Zizzari P, Longchamps R, Epelbaum J, Bluet-Pajot MT. Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents. Endocrinology 2007; 148(4): 1648-53.
[http://dx.doi.org/10.1210/en.2006-1231] [PMID: 17204551]
[20] Qi X, Li L, Yang G, et al. Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007; 66(4): 593-7.
[PMID: 17371480]
[21] Ma X, Zhao Y, Wang Q, et al. Plasma ghrelin concentrations are negatively correlated with urine albumin-to-creatinine ratio in newly diagnosed type 2 diabetes. Am J Med Sci 2014; 348(5): 382-6.
[http://dx.doi.org/10.1097/MAJ.0000000000000297] [PMID: 24875659]
[22] Taskin MI, Bulbul E, Adali E, Hismiogulları AA, Inceboz U. Circulating levels of obestatin and copeptin in obese and nonobese women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2015; 189: 19-23.
[http://dx.doi.org/10.1016/j.ejogrb.2015.03.006] [PMID: 25837320]
[23] Huang L, Tong Y, Zhang F, et al. Increased acyl ghrelin but decreased total ghrelin and unacyl ghrelin in Chinese Han people with impaired fasting glucose combined with impaired glucose tolerance. Peptides 2014; 60: 86-94.
[http://dx.doi.org/10.1016/j.peptides.2014.07.022] [PMID: 25102450]

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"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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