Amaç:
β hücrelerinin fonksiyonlarındaki değişiklikler polikistik over sendromunun (PCOS) patogenezinde önemli roller oynayabilir. Pankreatic Derived Factor (PANDER), patolojik koşullar altında pankreatik β hücre apoptozunu indükleyen sitokin benzeri bir proteindir. Bu araştırma, serum PANDER düzeylerini belirlemek ve serum PANDER düzeylerinin oksidatif stres ve PCOS'taki insülin direnci ile ilişkili olup olmadığını belirlemek için planlanmıştır.
Gereç ve Yöntem:
Bu kontrollü klinik çalışmada PKOS tanısı almış 27 hasta ve 24 sağlıklı kadın control grubu olarak değerlendirildi. Serum lipit alt fraksiyonları, açlık glikozu, insülin, gonadotropinler ve androjenler, malondialdehit (MDA) ve PANDER düzeyleri ölçüldü. İnsülin direncini tahmin etmek için homeostaz model değerlendirmesi (HOMA-IR) kullanıldı.
Bulgular:
Çalışma ve kontrol grubundaki denekler bel ölçümleri, gonadotropinler, lipit alt fraksiyonları, MDA ve PANDER düzeyleri açısından benzerdi, PKOS'lu kadınlar sağlıklı kadınlardan önemli ölçüde daha yüksek FAI ve HOMA-IR'ye sahipti. Serum PANDER düzeyleri çalışılan parametrelerle ilişkili değildi.
Sonuç:
Bu sonuçlar PANDER seviyesinin PCOS'ta insülin direnci, over kaynaklı hiperandrojenizm ve oksidatif stres ile ilişkili olmadığını göstermiştir.
1 Ehrmann DA. Medical progress: polycystic ovary syndrome. N Engl J Med 2004: 352: 1223–1236
2 Broekmans FJ, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser BC. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG. 2006; 113(10): 1210-1217.
3 Artimani T, Karimi J, Mehdizadeh M, et al. Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2018; 34(2): 148-152.
4 Mohammadi S, Kayedpoor P, Karimzadeh-Bardei L, Nabiuni M. The Effect of Curcumin on TNF-α, IL-6 and CRP Expression in a Model of Polycystic Ovary Syndrome as an Inflammation State. J Reprod Infertil. 2017; 18(4): 352-360.
5 Amer SAK. Polycystic ovarian syndrome: diagnosis and management of related infertility. Obstet Gynaecol Reprod Med. 2009; 19(10): 263-270.
6 González F. Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 2012; 77: 300-305.
7 Zhu Y, Xu GX, Patel A, et al. Cloning, expression and initial characterization of a novel cytokine like gene family. Genomics 2002; 80:144–150.
8 Cao X, Gao Z, Robert CE, et al. Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-cells. Diabetes. 2003; 52(9): 2296-2303.
9 Burkhardt BR, Greene SR, White P, et al. PANDER-induced cell-death genetic networks in islets reveal central role for caspase-3 and cyclin-dependent kinase inhibitor 1A (p21). Gene. 2006; 369: 134–141.
10 Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 2003; 80: 123-127.
11 Chen L, Xu WM, Zhang D. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome. Fertil Steril. 2014; 102(4): 1167-1174.
12 Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev. 2012; 70(5):257-65.
13 Blair SA, Kyaw-Tun T, Young IS, Phelan NA, Gibney J, McEneny J. Oxidative stress and inflammation in lean and obese subjects with polycystic ovary syndrome. J Reprod Med. 2013; 58(3-4): 107-114.
14 Robertson RP, Harmon J, Tran PO, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004; 53 Suppl 1: S119-124.
15 Wang J, Wang H. Oxidative Stress in Pancreatic Beta Cell Regeneration. Oxid Med Cell Longev. 2017: 1930261. doi: 10.1155/2017/1930261.
16 Wang H, Wang X, Zhu Y, Chen F, Sun Y, Han X. Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function. J Steroid Biochem Mol Biol. 2015; 154: 254-266.
17 Shoaei T, Heidari-Beni M, Tehrani HG, Feizi A, Esmaillzadeh A, Askari G. Effects of Probiotic Supplementation on Pancreatic β-cell Function and C-reactive Protein in Women with Polycystic Ovary Syndrome: A Randomized Double-blind Placebo-controlled Clinical Trial. Int J Prev Med. 2015; 6: 27.
19 Azziz R, Carmina E, Dewailly D, et al; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006; 91: 4237-4245.
20 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC Homeostasis model assessment: insulin resistance and β -cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419.
21 Levy JC, Matthews DR and Hermans MP (1998) Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21: 2191-2192.
22 Geloneze B, Vasques AC, Stabe CF, et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol 53: 281-287.
23 Okhawa H, Ohishi N. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358.
24 Wang C, Burkhardt BR, Guan Y, Yang J. Role of pancreatic-derived factor in type 2 diabetes: evidence from pancreatic β cells and liver. Nutr Rev. 2012; 70(2): 100-106.
25 Yang J, Gao Z, Robert CE, et al. Structure-function studies of PANDER, an islet specific cytokine inducing cell death of insulin-secreting beta cells. Biochemistry 2005; 44:11342–11352.
26 Wang O, Cai K, Pang S, et al. Mechanisms of glucose-induced expression of pancreatic-derived factor in pancreatic β-cells. Endocrinology 2008; 149: 672–680.
27 Shehata MM, Kamal MM, El-Hefnawy MH, El-Mesallamy HO. Association of serum pancreatic derived factor (PANDER) with beta-cell dysfunction in type 2 diabetes mellitus. J Diabetes Complications. 2017; 31(4): 748-752.
28 Wilson CG, Robert-Cooperman CE, Burkhardt BR. Pancreatic-Derived factor: novel hormone PANDERing to glucose regulation. FEBS Lett. 2011; 585(14): 2137-2143.
29 Hou X, Wang O, Li Z, et al. Upregulation of pancreatic derived factor (FAM3B) expression in pancreatic β-cells by MCP-1 (CCL2). Mol Cell Endocrinol. 2011; 343(1-2): 18-24.
30 Cieślak M, Wojtczak A, Cieślak M. Role of pro-inflammatory cytokines of pancreatic islets and prospects of elaboration of new methods for the diabetes treatment. Acta Biochim Pol. 2015; 62(1): 15-21.
31 Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005; 15: 316-28.
32 Rizzo M, Kotur-Stevuljevic J, Berneis K, et al. Atherogenic dyslipidemia and oxidative stress: a new look. Transl Res 2009; 153: 217-223.
33 Stuart D, Nagamani M. Acute augmentation of plasma androstenedione and dehydroepiandrosterone by euglycemic insulin infusion: evidence for a direct effect of insulin on ovarian steroidogenesis. 279-288. In: Dunaif A, Givens J, Haseltine F, Merriam G (Eds). Current issues in endocrinology and metabolism: polycystic ovary syndrome. Cambridge: Blackwell, 1992.
The evaluation of serum Pancreatic-derived factor and Malondialdehyde levels in patients with polycystic ovary syndrome
Purpose: Alterations in β-cell function may play crucial roles in the pathogenesis of polycystic ovary syndrome (PCOS). Pancreatic-derived factor (PANDER) is a cytokine-like protein, inducing of pancreatic β-cell apoptosis under pathological conditions. This investigation was planned to determine serum PANDER levels and establish whether serum PANDER levels are related with oxidative stress, and insulin resistance in PCOS.
Materials and Methods: Twenty-seven patients with PCOS and 24 healthy control women were evaluated in this controlled clinical study. Serum lipid sub-fractions, fasting glucose, insulin, gonadotropins, androgens, malondialdehyde (MDA) and PANDER levels were measured. Homeostasis model assessment (HOMA-IR) were used to estimate insulin resistance.
Results: Subjects in study and control groups were similar with respect to waist measurements, gonadotropins, lipid sub-fractions, MDA and PANDER levels, the women with PCOS had considerably higher FAI and HOMA-IR than healthy women. Serum PANDER levels were not correlated with any studied parameters.
Conclusion: These outcomes showed that PANDER level is not related with insulin resistance, ovarian hyperandrogenism and oxidative stress in PCOS.
1 Ehrmann DA. Medical progress: polycystic ovary syndrome. N Engl J Med 2004: 352: 1223–1236
2 Broekmans FJ, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser BC. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG. 2006; 113(10): 1210-1217.
3 Artimani T, Karimi J, Mehdizadeh M, et al. Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2018; 34(2): 148-152.
4 Mohammadi S, Kayedpoor P, Karimzadeh-Bardei L, Nabiuni M. The Effect of Curcumin on TNF-α, IL-6 and CRP Expression in a Model of Polycystic Ovary Syndrome as an Inflammation State. J Reprod Infertil. 2017; 18(4): 352-360.
5 Amer SAK. Polycystic ovarian syndrome: diagnosis and management of related infertility. Obstet Gynaecol Reprod Med. 2009; 19(10): 263-270.
6 González F. Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 2012; 77: 300-305.
7 Zhu Y, Xu GX, Patel A, et al. Cloning, expression and initial characterization of a novel cytokine like gene family. Genomics 2002; 80:144–150.
8 Cao X, Gao Z, Robert CE, et al. Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-cells. Diabetes. 2003; 52(9): 2296-2303.
9 Burkhardt BR, Greene SR, White P, et al. PANDER-induced cell-death genetic networks in islets reveal central role for caspase-3 and cyclin-dependent kinase inhibitor 1A (p21). Gene. 2006; 369: 134–141.
10 Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 2003; 80: 123-127.
11 Chen L, Xu WM, Zhang D. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome. Fertil Steril. 2014; 102(4): 1167-1174.
12 Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev. 2012; 70(5):257-65.
13 Blair SA, Kyaw-Tun T, Young IS, Phelan NA, Gibney J, McEneny J. Oxidative stress and inflammation in lean and obese subjects with polycystic ovary syndrome. J Reprod Med. 2013; 58(3-4): 107-114.
14 Robertson RP, Harmon J, Tran PO, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004; 53 Suppl 1: S119-124.
15 Wang J, Wang H. Oxidative Stress in Pancreatic Beta Cell Regeneration. Oxid Med Cell Longev. 2017: 1930261. doi: 10.1155/2017/1930261.
16 Wang H, Wang X, Zhu Y, Chen F, Sun Y, Han X. Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function. J Steroid Biochem Mol Biol. 2015; 154: 254-266.
17 Shoaei T, Heidari-Beni M, Tehrani HG, Feizi A, Esmaillzadeh A, Askari G. Effects of Probiotic Supplementation on Pancreatic β-cell Function and C-reactive Protein in Women with Polycystic Ovary Syndrome: A Randomized Double-blind Placebo-controlled Clinical Trial. Int J Prev Med. 2015; 6: 27.
19 Azziz R, Carmina E, Dewailly D, et al; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006; 91: 4237-4245.
20 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC Homeostasis model assessment: insulin resistance and β -cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419.
21 Levy JC, Matthews DR and Hermans MP (1998) Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21: 2191-2192.
22 Geloneze B, Vasques AC, Stabe CF, et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol 53: 281-287.
23 Okhawa H, Ohishi N. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358.
24 Wang C, Burkhardt BR, Guan Y, Yang J. Role of pancreatic-derived factor in type 2 diabetes: evidence from pancreatic β cells and liver. Nutr Rev. 2012; 70(2): 100-106.
25 Yang J, Gao Z, Robert CE, et al. Structure-function studies of PANDER, an islet specific cytokine inducing cell death of insulin-secreting beta cells. Biochemistry 2005; 44:11342–11352.
26 Wang O, Cai K, Pang S, et al. Mechanisms of glucose-induced expression of pancreatic-derived factor in pancreatic β-cells. Endocrinology 2008; 149: 672–680.
27 Shehata MM, Kamal MM, El-Hefnawy MH, El-Mesallamy HO. Association of serum pancreatic derived factor (PANDER) with beta-cell dysfunction in type 2 diabetes mellitus. J Diabetes Complications. 2017; 31(4): 748-752.
28 Wilson CG, Robert-Cooperman CE, Burkhardt BR. Pancreatic-Derived factor: novel hormone PANDERing to glucose regulation. FEBS Lett. 2011; 585(14): 2137-2143.
29 Hou X, Wang O, Li Z, et al. Upregulation of pancreatic derived factor (FAM3B) expression in pancreatic β-cells by MCP-1 (CCL2). Mol Cell Endocrinol. 2011; 343(1-2): 18-24.
30 Cieślak M, Wojtczak A, Cieślak M. Role of pro-inflammatory cytokines of pancreatic islets and prospects of elaboration of new methods for the diabetes treatment. Acta Biochim Pol. 2015; 62(1): 15-21.
31 Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005; 15: 316-28.
32 Rizzo M, Kotur-Stevuljevic J, Berneis K, et al. Atherogenic dyslipidemia and oxidative stress: a new look. Transl Res 2009; 153: 217-223.
33 Stuart D, Nagamani M. Acute augmentation of plasma androstenedione and dehydroepiandrosterone by euglycemic insulin infusion: evidence for a direct effect of insulin on ovarian steroidogenesis. 279-288. In: Dunaif A, Givens J, Haseltine F, Merriam G (Eds). Current issues in endocrinology and metabolism: polycystic ovary syndrome. Cambridge: Blackwell, 1992.
Çabuş Ü, Kaleli B, Fenkci İ, Kaleli İ, Demir S. The evaluation of serum Pancreatic-derived factor and Malondialdehyde levels in patients with polycystic ovary syndrome. Pam Tıp Derg. Eylül 2020;13(3):715-721. doi:10.31362/patd.699953