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Circulating galanin levels are increased in patients with gestational diabetes mellitus
Clinical Biochemistry 46 (2013) 831–833
Contents lists available at SciVerse ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Short Communication
Circulating galanin levels are increased in patients with gestational diabetes mellitus Penghua Fang a, Ping Bo c, Mingyi Shi c, Mei Yu c, Zhenwen Zhang b, c,⁎ a b c
Department of Physiology, School of Hanlin, Nanjing University of Chinese Medicine, Taizhou, Jiangsu 225300, China Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China Research Institution of Combining Chinese Traditional and Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China
a r t i c l e
i n f o
Article history: Received 17 July 2012 Received in revised form 12 December 2012 Accepted 13 December 2012 Available online 22 December 2012 Keywords: Galanin Glucose Gestational diabetes
a b s t r a c t Background: Galanin is a 29/30-amino acid peptide that stimulates food intake and regulates energy metabolism. A significantly higher level of plasma galanin was found in diabetes in non-pregnant women, but there are no data regarding galanin levels in diabetes in pregnant women. In this study we compared plasma galanin concentrations in pregnant women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Material and methods: The study registered twenty pregnant women with GDM and twenty pregnant women with NGT. Fasting venous blood samples were collected from all cases. Galanin was analyzed by an enzyme-linked immunosorbent assay. Results: A statistically significant higher level of galanin was found in pregnant women with GDM compared with NGT (P b 0.001). In addition, a significant positive correlation was shown between galanin and glucose (P b 0.001), galanin and BMI (P = 0.008) in pregnant women with GDM, although there was no association between galanin and insulin and/or galanin and HbA1c. Conclusions: Circulating galanin levels are higher in patients with GDM. Circulating galanin levels appear to be related to the changes of blood glucose in GDM. The higher level of galanin observed in GDM may represent a physiological adaptation to the rise of glucose associated with GDM. © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Introduction Galanin, a 29/30-amino-acid peptide, was first isolated in 1983 from porcine intestine by Tatemoto and collaborators [1]. It is synthesized in the central and peripheral nervous systems, and also commonly expressed in peripheral tissues to modulate food intake, energy metabolism, pain threshold and reproduction [2]. As yet, three types of galanin receptors (GalR1, GalR2, and GalR3) widely distributed in the nervous system and pancreas as well as gut have been identified by molecular cloning and characterized pharmacologically in various species [2]. Recent studies provided clues on the relationship between galanin and glucose homeostasis [3,4]. In particular, galanin can directly inhibit glucose-stimulated insulin release in animals and humans [4,5]. Besides, elevated plasma galanin levels were found in patients with obesity, type 1 diabetes and type 2 diabetes [5–7]. It also regulates circulating glucose levels by reducing insulin resistance and stimulating glucose uptake through the acceleration of the translocation of glucose transporter 4 to the plasma membrane of various insulin-sensitive cells [8,9]. In addition, a strong positive correlation
⁎ Corresponding author at: Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China. Fax: +86 514 87341733. E-mail address: [email protected] (Z. Zhang).
of galanin has been established with fasting glucose in type 2 diabetes [5]. In children with type 1 diabetes, a positive correlation was found between galanin and hemoglobin A1c (HbA1c) [7], which may be an important predictive factor in GDM pregnancies. Based on these recent studies, it appears that galanin might have a role in regulating glucose, insulin and HbA1c metabolism and it also may influence gestational diabetes mellitus. Gestational diabetes mellitus (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy [10]. The most widely accepted explanation for GDM is associated with physiological changes that include an increase in food intake and body weight as well as a progressive increase in glucose and insulin resistance. As there are no data regarding galanin levels in GDM patients during pregnancy period, the present study aims to evaluate plasma galanin concentration in pregnant women with normal glucose tolerance (NGT) and GDM and to find out whether or not it has a role in the pathophysiology of GDM. Material and method The present study was conducted in the Clinical Medical College, Yangzhou University, after the approval of the ethics committee dated May 2011. The present study consisted of 20 pregnant women with GDM and 20 pregnant women with normal glucose
0009-9120/$ – see front matter © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clinbiochem.2012.12.013
832
P. Fang et al. / Clinical Biochemistry 46 (2013) 831–833
tolerance (NGT) and without a family history of diabetes. Women with preeclampsia and other pregnancy complications (except GDM) were excluded from the study. Written consents of all participants were obtained and the protocol of the study was approved by the local ethics committee (Medical College, Yangzhou University). All subjects were given 100 g oral glucose tolerance test (OGTT) at 8:00 A.M. after overnight fasting. GDM was diagnosed according to the American Diabetes Association criteria [fasting plasma glucose≥95 mg/dL (5.3 mmol/L), 1-hour plasma glucose ≥ 180 mg/dL (10 mmol/L), 2-hour plasma glucose ≥ 155 mg/dL (8.6 mmol/L) and 3-hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L)]. Plasma glucose concentrations were measured using oxidase method. Plasma insulin levels were measured by radioimmunoassay (China Institute of Atomic Energy, Beijing, China). HbA1c was evaluated by a high performance liquid chromatography technique (HPLC VariantTM, Bio-Rad, Germany). For each case body mass index (BMI) was calculated at the time of blood collection as weight in kilograms divided by height in meters squared. Blood sample handling and peptide assay Fasting venous blood samples were collected from all cases in the study in the first visit (upon diagnosis) in order to determine levels of galanin, glucose, fasting plasma insulin, and HbA1c. The blood samples (2 mL) were collected in prechilled EDTA tubes containing aprotinin and were immediately centrifuged for 15 min at 1000 ×g at 4 °C within 30 min of collection. Plasma was separated into vials and stored at − 80 °C until measurement. Galanin was analyzed by an enzyme-linked immunosorbent assay (Uscn Life Science, Inc. Wuhan, China). All measurements were performed in duplicate, and the mean of the two measurements was considered. According to the manufacturer's specification, the range of the assay was 12.35– 1000 pg/mL, and the average sensitivity was 4.21 pg/mL. Statistical analysis Statistical analysis was performed using the SPSS statistical software for Windows (Version 10.0). Data for each respective study were presented as mean ± SD. The differences between the groups were compared by the Kruskal–Wallis ANOVA with the Dunn's multiple-comparisons test. Possible correlations between parameters were evaluated by Spearman's correlation coefficient analyses. P b 0.05 was regarded as statistically significant. Results The study registered 20 pregnant women with GDM and 20 pregnant women with NGT. The results showed no significant differences in fasting insulin (12.97 ± 5.46 vs. 11.86 ± 3.09, P = 0.339), HbA1c (5.2 ± 0.25% vs. 4.9 ± 0.3%, P = 0.12), and BMI (30.65 ± 2.13 kg/m 2 vs. 29.54 ± 2.07 kg/m 2, P = 0.465) between the pregnant women with GDM and NGT, whereas fasting glucose was significantly higher in the pregnant women with GDM (P b 0.001) (see Table 1).
Interestingly, a statistically significant higher level of galanin was found in pregnant women with GDM compared with NGT (36.97 ± 12.52 pg/mL vs. 15.53 ± 4.48 pg/mL, P b 0.001) (see Fig. 1). In addition, a significant positive correlation was shown between galanin and glucose (r = 0.948, P b 0.001) and galanin and BMI (r = 0.556, P = 0.008) in pregnant women with GDM, whereas there was no association between galanin and insulin (r = − 0.035, P = 0.882), and galanin and HbA1c (r = 0.317, P = 0.173) in the same group. In NGT group there were no significant correlations between galanin and any of the anthropometric or metabolic parameters studied.
Discussion Whereas the neuropeptide galanin is undoubtedly a regulator of glucose metabolism and homeostasis [3–5], studies in animal and human indicate that galanin also plays an important role in the regulation of insulin release and insulin sensitivity [4,8,9]. To our best knowledge, there are no other data concerning galanin concentrations in pregnant women with GDM. The present study shows that a statistically significant higher level of galanin was found in pregnant women with GDM compared with NGT. Also, a positive correlation was found between galanin and glucose, and galanin and BMI in pregnant women with GDM. Galanin did not correlate with insulin and HbA1c in GDM and NGT. Numerous studies provided clues on the close relationship between galanin and glucose. During glucose tolerance tests, galanin gene-knockout mice experienced impaired glucose disposal caused by a reduction in insulin response and insulin-independent glucose elimination [11]. Legakis et al. reported that a significantly higher level of plasma galanin was found in non-pregnant women with type 2 diabetes [5]. Moreover, the level of galanin was positively correlated with blood glucose in non-pregnant women with diabetes [5]. In addition, a positive correlation between blood glucose content and galanin levels was observed (in the fasting state) in healthy volunteers during the glucose tolerance test [12]. Consistent with observations of others studying type 1 diabetes and type 2 diabetes [5,7], we noted that GDM subjects have higher plasma concentrations of galanin than NGT control subjects. Besides, a positive correlation between blood glucose content and galanin levels was observed. These data seem to indicate that the upregulation of galanin may be a consequence of elevated glucose, because higher level of plasma galanin is positively correlated with higher level of blood glucose in the pregnant women with GDM. Recent studies demonstrate that hypothalamic galanin exerts an orexigenic effect in animals [6]. In addition to feeding behavior, galanin affects the metabolism, which causes a reduction in energy expenditure and the sympathetic activation of brown adipose tissue [6]. In return, BMI may modulate plasma galanin levels of animals too. The higher level of galanin was observed in the plasma of fat
Table 1 Demographic and biochemical characteristics of study and control groups.
N Age (years) BMI (kg/m2) HbA1c (%) Glucose (mmol/L) Insulin (μIU/mL)
GDM
NGT
P value
20 28.98 ± 3.38 30.65 ± 2.13 5.2 ± 0.25% 5.72 ± 1.14 12.97 ± 5.46
20 27.10 ± 4.48 29.54 ± 2.07 4.9 ± 0.3% 3.75 ± 0.22 11.86 ± 3.09
0.112 0.465 0.12 b0.001 0.339
Results are shown as means ± SD; statistical significance P b 0.05; N, number of cases.
Fig. 1. Plasma galanin level in patients with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Data are expressed as mean ± SD, △△P b 0.001 GDM vs. NGT.
P. Fang et al. / Clinical Biochemistry 46 (2013) 831–833
men compared with that in the thin men [13,14]. Interestingly, only in the GDM a statistical correlation of galanin with BMI was found, although there was no difference between BMI of GDM and that of NGT. Therefore, the statistical correlation of galanin with BMI in the GDM might be due to the effect of BMI in the glucose levels on GDM. There is a growing body of evidence that indicates a suppressive role of galanin in the release of insulin from the pancreatic islets in animals. Galanin and its fragment galanin (1–15) NH2 inhibit glucose-induced or basal insulin secretion in vivo and in vitro [15,16]. Meanwhile, Tang et al. demonstrated that galanin inhibits insulin secretion in the pancreas from the islets of pancreatic tissue via the activation of G(o)2 of the G(i/o) protein family [17]. Interestingly, our analysis suggests that galanin did not correlate with insulin and HbA1c in both GDM and NGT, which is opposite to that of Legakis et al. who found that the higher level of galanin in type 2 diabetes exhibited strong positive correlation with HbA1c levels [5]. The possible reason why galanin did not correlate with insulin and HbA1c is insulin resistance. Because it is known that slight insulin resistance develops during pregnancy with GDM [10]. This slight insulin resistance in pregnant women may contribute to our failure to find a statistically significant difference. In conclusion, circulating galanin levels are higher and appear to be related to the changes of blood glucose in GDM. The higher level of galanin observed in GDM may represent a physiological adaptation to the rise of glucose associated with GDM. Careful prospective clinical studies with large study populations and long follow-up time are now necessary to further clarify the role of galanin in the pathogenesis of the GDM. Conflict of interest statement The authors declare that there are no conflicts of interest. Acknowledgments This work was supported by the Grant of National Natural Scientific Fund of China in year 2011 to Ping Bo, PhD (81173392).
833
References [1] Tatemoto K, Rökaeus A, Jörnvall H, McDonald TJ, Mutt V. Galanin-a novel biologically active peptide from porcine intestine. FEBS Lett 1983;164:124–8. [2] Lang R, Gundlach AL, Kofler B. The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease. Pharmacol Ther 2007;115:177–207. [3] Legakis IN. The role of galanin in metabolic disorders leading to type 2 diabetes mellitus. Drug News Perspect 2005;18:173–7. [4] Zhang Z, Sheng S, Guo L, et al. Intracerebroventricular administration of galanin antagonist sustains insulin resistance in adipocytes of type 2 diabetic trained rats. Mol Cell Endocrinol 2012;361:213–8. [5] Legakis I, Mantzouridis T, Mountokalakis T. Positive correlation of galanin with glucose in type 2 diabetes. Diabetes Care 2005;28:759–60. [6] Fang P, Yu M, Guo L, Bo P, Zhang Z, Shi M. Galanin and its receptors: a novel strategy for appetite control and obesity therapy. Peptides 2012;36:331–9. [7] Celi F, Bini V, Papi F, et al. Circulating acylated and total ghrelin and galanin in children with insulin-treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development. Clin Endocrinol (Oxf) 2005;63:139–45. [8] He B, Shi M, Zhang L, et al. Beneficial effect of galanin on insulin sensitivity in muscle of type 2 diabetic rats. Physiol Behav 2011;103:284–9. [9] Liang Y, Sheng S, Fang P, et al. Exercise-induced galanin release facilitated GLUT4 translocation in adipocytes of type 2 diabetic rats. Pharmacol Biochem Behav 2012;100:554–9. [10] Petry CJ. Gestational diabetes: risk factors and recent advances in its genetics and treatment. Br J Nutr 2010;104:775–87. [11] Ahrén B, Pacini G, Wynick D, Wierup N, Sundler F. Loss-of-function mutation of the galanin gene is associated with perturbed islet function in mice. Endocrinology 2004;145:3190–6. [12] Legalkis IN, Mantzouridis T, Mountokalakis T. Positive correlation of galanin with glucose in healthy volunteers during an oral glucose tolerance test. Horm Metab Res 2007;39:53–5. [13] Baranowska B, Wasilewska-Dziubińska E, Radzikowska M, Plonowski A, Roguski K. Neuropeptide Y, galanin, and leptin release in obese women and in women with anorexia nervosa. Metabolism 1997;46:1384–9. [14] Baranowska B, Radzikowska M, Wasilewska-Dziubinska E, Roguski K, Borowiec M. Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity. Diabetes Obes Metab 2000;2:99–103. [15] Manabe T, Okada Y, Sawai H, et al. Effect of galanin on plasma glucose, insulin and pancreatic glucagon in dogs. J Int Med Res 2003;31:126–32. [16] Ruczyński J, Cybal M, Wójcikowski C, Rekowski P. Effects of porcine galanin, galanin(1–15)NH2 and its new analogues on glucose-induced insulin secretion. Pol J Pharmacol 2002;54:133–41. [17] Tang G, Wang Y, Park S, et al. Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic β cells. Proc Natl Acad Sci U S A 2012;109: 2636–41.
Contents lists available at SciVerse ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Short Communication
Circulating galanin levels are increased in patients with gestational diabetes mellitus Penghua Fang a, Ping Bo c, Mingyi Shi c, Mei Yu c, Zhenwen Zhang b, c,⁎ a b c
Department of Physiology, School of Hanlin, Nanjing University of Chinese Medicine, Taizhou, Jiangsu 225300, China Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China Research Institution of Combining Chinese Traditional and Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China
a r t i c l e
i n f o
Article history: Received 17 July 2012 Received in revised form 12 December 2012 Accepted 13 December 2012 Available online 22 December 2012 Keywords: Galanin Glucose Gestational diabetes
a b s t r a c t Background: Galanin is a 29/30-amino acid peptide that stimulates food intake and regulates energy metabolism. A significantly higher level of plasma galanin was found in diabetes in non-pregnant women, but there are no data regarding galanin levels in diabetes in pregnant women. In this study we compared plasma galanin concentrations in pregnant women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Material and methods: The study registered twenty pregnant women with GDM and twenty pregnant women with NGT. Fasting venous blood samples were collected from all cases. Galanin was analyzed by an enzyme-linked immunosorbent assay. Results: A statistically significant higher level of galanin was found in pregnant women with GDM compared with NGT (P b 0.001). In addition, a significant positive correlation was shown between galanin and glucose (P b 0.001), galanin and BMI (P = 0.008) in pregnant women with GDM, although there was no association between galanin and insulin and/or galanin and HbA1c. Conclusions: Circulating galanin levels are higher in patients with GDM. Circulating galanin levels appear to be related to the changes of blood glucose in GDM. The higher level of galanin observed in GDM may represent a physiological adaptation to the rise of glucose associated with GDM. © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Introduction Galanin, a 29/30-amino-acid peptide, was first isolated in 1983 from porcine intestine by Tatemoto and collaborators [1]. It is synthesized in the central and peripheral nervous systems, and also commonly expressed in peripheral tissues to modulate food intake, energy metabolism, pain threshold and reproduction [2]. As yet, three types of galanin receptors (GalR1, GalR2, and GalR3) widely distributed in the nervous system and pancreas as well as gut have been identified by molecular cloning and characterized pharmacologically in various species [2]. Recent studies provided clues on the relationship between galanin and glucose homeostasis [3,4]. In particular, galanin can directly inhibit glucose-stimulated insulin release in animals and humans [4,5]. Besides, elevated plasma galanin levels were found in patients with obesity, type 1 diabetes and type 2 diabetes [5–7]. It also regulates circulating glucose levels by reducing insulin resistance and stimulating glucose uptake through the acceleration of the translocation of glucose transporter 4 to the plasma membrane of various insulin-sensitive cells [8,9]. In addition, a strong positive correlation
⁎ Corresponding author at: Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China. Fax: +86 514 87341733. E-mail address: [email protected] (Z. Zhang).
of galanin has been established with fasting glucose in type 2 diabetes [5]. In children with type 1 diabetes, a positive correlation was found between galanin and hemoglobin A1c (HbA1c) [7], which may be an important predictive factor in GDM pregnancies. Based on these recent studies, it appears that galanin might have a role in regulating glucose, insulin and HbA1c metabolism and it also may influence gestational diabetes mellitus. Gestational diabetes mellitus (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy [10]. The most widely accepted explanation for GDM is associated with physiological changes that include an increase in food intake and body weight as well as a progressive increase in glucose and insulin resistance. As there are no data regarding galanin levels in GDM patients during pregnancy period, the present study aims to evaluate plasma galanin concentration in pregnant women with normal glucose tolerance (NGT) and GDM and to find out whether or not it has a role in the pathophysiology of GDM. Material and method The present study was conducted in the Clinical Medical College, Yangzhou University, after the approval of the ethics committee dated May 2011. The present study consisted of 20 pregnant women with GDM and 20 pregnant women with normal glucose
0009-9120/$ – see front matter © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clinbiochem.2012.12.013
832
P. Fang et al. / Clinical Biochemistry 46 (2013) 831–833
tolerance (NGT) and without a family history of diabetes. Women with preeclampsia and other pregnancy complications (except GDM) were excluded from the study. Written consents of all participants were obtained and the protocol of the study was approved by the local ethics committee (Medical College, Yangzhou University). All subjects were given 100 g oral glucose tolerance test (OGTT) at 8:00 A.M. after overnight fasting. GDM was diagnosed according to the American Diabetes Association criteria [fasting plasma glucose≥95 mg/dL (5.3 mmol/L), 1-hour plasma glucose ≥ 180 mg/dL (10 mmol/L), 2-hour plasma glucose ≥ 155 mg/dL (8.6 mmol/L) and 3-hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L)]. Plasma glucose concentrations were measured using oxidase method. Plasma insulin levels were measured by radioimmunoassay (China Institute of Atomic Energy, Beijing, China). HbA1c was evaluated by a high performance liquid chromatography technique (HPLC VariantTM, Bio-Rad, Germany). For each case body mass index (BMI) was calculated at the time of blood collection as weight in kilograms divided by height in meters squared. Blood sample handling and peptide assay Fasting venous blood samples were collected from all cases in the study in the first visit (upon diagnosis) in order to determine levels of galanin, glucose, fasting plasma insulin, and HbA1c. The blood samples (2 mL) were collected in prechilled EDTA tubes containing aprotinin and were immediately centrifuged for 15 min at 1000 ×g at 4 °C within 30 min of collection. Plasma was separated into vials and stored at − 80 °C until measurement. Galanin was analyzed by an enzyme-linked immunosorbent assay (Uscn Life Science, Inc. Wuhan, China). All measurements were performed in duplicate, and the mean of the two measurements was considered. According to the manufacturer's specification, the range of the assay was 12.35– 1000 pg/mL, and the average sensitivity was 4.21 pg/mL. Statistical analysis Statistical analysis was performed using the SPSS statistical software for Windows (Version 10.0). Data for each respective study were presented as mean ± SD. The differences between the groups were compared by the Kruskal–Wallis ANOVA with the Dunn's multiple-comparisons test. Possible correlations between parameters were evaluated by Spearman's correlation coefficient analyses. P b 0.05 was regarded as statistically significant. Results The study registered 20 pregnant women with GDM and 20 pregnant women with NGT. The results showed no significant differences in fasting insulin (12.97 ± 5.46 vs. 11.86 ± 3.09, P = 0.339), HbA1c (5.2 ± 0.25% vs. 4.9 ± 0.3%, P = 0.12), and BMI (30.65 ± 2.13 kg/m 2 vs. 29.54 ± 2.07 kg/m 2, P = 0.465) between the pregnant women with GDM and NGT, whereas fasting glucose was significantly higher in the pregnant women with GDM (P b 0.001) (see Table 1).
Interestingly, a statistically significant higher level of galanin was found in pregnant women with GDM compared with NGT (36.97 ± 12.52 pg/mL vs. 15.53 ± 4.48 pg/mL, P b 0.001) (see Fig. 1). In addition, a significant positive correlation was shown between galanin and glucose (r = 0.948, P b 0.001) and galanin and BMI (r = 0.556, P = 0.008) in pregnant women with GDM, whereas there was no association between galanin and insulin (r = − 0.035, P = 0.882), and galanin and HbA1c (r = 0.317, P = 0.173) in the same group. In NGT group there were no significant correlations between galanin and any of the anthropometric or metabolic parameters studied.
Discussion Whereas the neuropeptide galanin is undoubtedly a regulator of glucose metabolism and homeostasis [3–5], studies in animal and human indicate that galanin also plays an important role in the regulation of insulin release and insulin sensitivity [4,8,9]. To our best knowledge, there are no other data concerning galanin concentrations in pregnant women with GDM. The present study shows that a statistically significant higher level of galanin was found in pregnant women with GDM compared with NGT. Also, a positive correlation was found between galanin and glucose, and galanin and BMI in pregnant women with GDM. Galanin did not correlate with insulin and HbA1c in GDM and NGT. Numerous studies provided clues on the close relationship between galanin and glucose. During glucose tolerance tests, galanin gene-knockout mice experienced impaired glucose disposal caused by a reduction in insulin response and insulin-independent glucose elimination [11]. Legakis et al. reported that a significantly higher level of plasma galanin was found in non-pregnant women with type 2 diabetes [5]. Moreover, the level of galanin was positively correlated with blood glucose in non-pregnant women with diabetes [5]. In addition, a positive correlation between blood glucose content and galanin levels was observed (in the fasting state) in healthy volunteers during the glucose tolerance test [12]. Consistent with observations of others studying type 1 diabetes and type 2 diabetes [5,7], we noted that GDM subjects have higher plasma concentrations of galanin than NGT control subjects. Besides, a positive correlation between blood glucose content and galanin levels was observed. These data seem to indicate that the upregulation of galanin may be a consequence of elevated glucose, because higher level of plasma galanin is positively correlated with higher level of blood glucose in the pregnant women with GDM. Recent studies demonstrate that hypothalamic galanin exerts an orexigenic effect in animals [6]. In addition to feeding behavior, galanin affects the metabolism, which causes a reduction in energy expenditure and the sympathetic activation of brown adipose tissue [6]. In return, BMI may modulate plasma galanin levels of animals too. The higher level of galanin was observed in the plasma of fat
Table 1 Demographic and biochemical characteristics of study and control groups.
N Age (years) BMI (kg/m2) HbA1c (%) Glucose (mmol/L) Insulin (μIU/mL)
GDM
NGT
P value
20 28.98 ± 3.38 30.65 ± 2.13 5.2 ± 0.25% 5.72 ± 1.14 12.97 ± 5.46
20 27.10 ± 4.48 29.54 ± 2.07 4.9 ± 0.3% 3.75 ± 0.22 11.86 ± 3.09
0.112 0.465 0.12 b0.001 0.339
Results are shown as means ± SD; statistical significance P b 0.05; N, number of cases.
Fig. 1. Plasma galanin level in patients with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Data are expressed as mean ± SD, △△P b 0.001 GDM vs. NGT.
P. Fang et al. / Clinical Biochemistry 46 (2013) 831–833
men compared with that in the thin men [13,14]. Interestingly, only in the GDM a statistical correlation of galanin with BMI was found, although there was no difference between BMI of GDM and that of NGT. Therefore, the statistical correlation of galanin with BMI in the GDM might be due to the effect of BMI in the glucose levels on GDM. There is a growing body of evidence that indicates a suppressive role of galanin in the release of insulin from the pancreatic islets in animals. Galanin and its fragment galanin (1–15) NH2 inhibit glucose-induced or basal insulin secretion in vivo and in vitro [15,16]. Meanwhile, Tang et al. demonstrated that galanin inhibits insulin secretion in the pancreas from the islets of pancreatic tissue via the activation of G(o)2 of the G(i/o) protein family [17]. Interestingly, our analysis suggests that galanin did not correlate with insulin and HbA1c in both GDM and NGT, which is opposite to that of Legakis et al. who found that the higher level of galanin in type 2 diabetes exhibited strong positive correlation with HbA1c levels [5]. The possible reason why galanin did not correlate with insulin and HbA1c is insulin resistance. Because it is known that slight insulin resistance develops during pregnancy with GDM [10]. This slight insulin resistance in pregnant women may contribute to our failure to find a statistically significant difference. In conclusion, circulating galanin levels are higher and appear to be related to the changes of blood glucose in GDM. The higher level of galanin observed in GDM may represent a physiological adaptation to the rise of glucose associated with GDM. Careful prospective clinical studies with large study populations and long follow-up time are now necessary to further clarify the role of galanin in the pathogenesis of the GDM. Conflict of interest statement The authors declare that there are no conflicts of interest. Acknowledgments This work was supported by the Grant of National Natural Scientific Fund of China in year 2011 to Ping Bo, PhD (81173392).
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