Serum levels of pigment epithelium‐derived factor (PEDF) are positively associated with visceral adiposity in Japanese patients with type 2 diabetes

Nakamura, Kazuo; Yamagishi, Sho Ichi; Adachi, Hisashi; Kurita-Nakamura, Yayoi; Matsui, Takanori; Inoue, Hirokazu

doi:10.1002/dmrr.820

Cited by 66 publications

(68 citation statements)

References 17 publications

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“…Surface plasmon resonance analysis demonstrated that emetine binds to PEDF receptor ATGL with high-binding affinity (KD = 14.3 nmol/L) ( Figure 3A). (33), and PEDF levels are significantly associated with various metabolic diseases (25,(34)(35)(36). In the present results from murine streptozotocininduced diabetes, PEDF and TNF levels are significantly increased in pancreas, and expression significantly correlated with blood glucose levels.…”

Section: Emetine Binds Atgl With High Affinitysupporting

confidence: 53%

“…Elevated levels of PEDF have been observed in humans with type 2 diabetes mellitus, obesity, metabolic syndrome, vascular inflammation and cardiovascular diseases (25)(26)(27). In type 1 diabetes patients, microvascular complications, vascular stiffness, inflammation and diabetic retinopathy have been significantly correlated with increased serum levels of PEDF (28,29).…”

Section: Histologymentioning

confidence: 99%

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Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Hudson

Dancho

et al. 2016

Mol Med

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Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by β cell destruction, insulin deficiency and hyperglycemia. Activated macrophages and autoimmune T cells play a crucial role in the pathogenesis of hyperglycemia in NOD murine diabetes models, but the molecular mechanisms of macrophage activation are unknown. We recently identified pigment epithelium-derived factor (PEDF) as an adipocyte-derived factor that activates macrophages and mediates insulin resistance. Reasoning that PEDF might participate as a proinflammatory mediator in murine diabetes, we measured PEDF levels in NOD mice. PEDF levels are significantly elevated in pancreas, in parallel with pancreatic TNF levels in NOD mice. To identify experimental therapeutics, we screened 2,327 compounds in two chemical libraries (the NIH Clinical Collection and Pharmakon-1600) for leads that inhibit PEDF mediated TNF release in macrophage cultures. The lead molecule selected, "emetine" is a widely used emetic. It inhibited PEDF-mediated macrophage activation with an EC50 or 146 nmol/L. Administration of emetine to NOD mice and to C57Bl6 mice subjected to streptozotocin significantly attenuated hyperglycemia, reduced TNF levels in pancreas and attenuated insulitis. Together, these results suggest that targeting PEDF with emetine may attenuate TNF release and hyperglycemia in murine diabetes models. This suggests that further investigation of PEDF and emetine in the pathogenesis of human diabetes is warranted.

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Section: Emetine Binds Atgl With High Affinitysupporting

confidence: 53%

Section: Histologymentioning

confidence: 99%

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Hudson

Dancho

et al. 2016

Mol Med

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“…Much less is known regarding the antiangiogenic factors secreted locally and the role they play in the regulation of angiogenesis in expanding adipose tissue. PEDF is a major endogenous inhibitor of angiogenesis, circulating levels of PEDF are tightly correlated with obesity (25,26,30,32,37,38), and adipocytes are a major source of PEDF (13,20). Studies of human primary adipocytes have demonstrated that PEDF secretion is eightfold greater than adiponectin secretion and 140-fold greater than VEGF secretion (20).…”

Section: Discussionmentioning

confidence: 99%

Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements

Lakeland

Borg

Matzaris

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Lakeland TV, Borg ML, Matzaris M, Abdelkader A, Evans RG, Watt MJ. Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements. Am J Physiol Endocrinol Metab 306: E1367-E1377, 2014. First published April 23, 2014; doi:10.1152/ajpendo.00046.2014.-Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O 2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo. pigment epithelium-derived factor; lipolysis; obesity; insulin sensitivity ADIPOCYTES SECRETE PROTEINS AND METABOLITES that play major roles in the regulation of metabolism, appetite, energy expenditure, and inflammation.

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“…(29) This was against a study made by Li et al . (30) who investigate serum PEDF levels in GDM women there was no correlation between PEDF concentration with age, week of gestation, prepregnancy BMI, and blood lipids levels.…”

Section: Table1mentioning

confidence: 71%

Serum pigment epithelium derived factor as a new marker in the metabolic syndrome

Sabry¹,

Shaaer²,

Hammady³

2017

Int J Recent Sci Res

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Background: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hyperglycemia, hypertension, dyslipidemia, and insulin resistance, with insulin resistance and central obesity in particular recognized as causative factors. Aim of the study: to determine serum level of Serum pigment epithelium derived factor (PEDF) and to examine whether PEDF serum level are associated with metabolic syndrome risk factor. Materials and Methods: The present study was conducted on 90 subjects subdivided into two groups. Patient group included 70 patients with metabolic syndrome attending the outpatient clinic in Benha University Hospital. and control group, this group included 20 apparently healthy individuals, Blood samples were drawn from all subjects to assess serum levels of PEDF, Hs-CRP, lipid profile, F.B.S, creatinine and uric acid. Results: PEDF level was significantly higher in patient group than control group, significant elevation of Hs-CRP, FBS, TG, LDL-cholesterol and uric acid in patient group versus control group and significant decrease of HDL-cholesterol in patient group versus control group. Significant positive correlation between PEDF (patient group) and each of the components of Metabolic syndromeas BMI,WC, LDL-cholesterol and total cholesterol, triglyceride, systolic &diastolic blood pressure and the accumulation of the number of this component collectively. Conclusion: Based on the evidence presented within the study, PEDF correlate significantly with metabolic syndrome and could provide a minimally-invasive mean for early detection and specific treatment of this disorder. Further research is encouraged to determine the efficacy of applying this biomarker fordiagnosis of metabolic syndrome.

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Serum levels of pigment epithelium‐derived factor (PEDF) are positively associated with visceral adiposity in Japanese patients with type 2 diabetes

Cited by 66 publications

References 17 publications

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements

Serum pigment epithelium derived factor as a new marker in the metabolic syndrome

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