Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients

Jenkins, Alicia J.; Fu, Dongxu; Azar, Madona; Stoner, Julie A.; Kaufman, Derrick; Zhang, Sarah; Klein, Richard L.; Lopes‐Virella, Maria F.; Xing, Jian; Lyons, Timothy J.

doi:10.1016/j.jdiacomp.2014.01.008

Cited by 20 publications

(20 citation statements)

References 49 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: 52%

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: 52%

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Hudson

Dancho

et al. 2016

Mol Med

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“…Pigment epithelial-derived factor (PEDF) is a serpin-like protein lacking inhibitory function that was selected for study because expression is known to be influenced by diabetes and obesity [ 2 , 3 ], circulating levels are related to vascular complications of diabetes and insulin sensitivity [ 4 – 6 ], and it is produced by adipose tissue, liver, and placenta [ 7 – 9 ]. One prior report found PEDF expression decreased in placentae from stillborn [ 10 ] and a pilot study noted increased cord blood levels in pre-eclampsia [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus

Teague

Fields

Aston

et al. 2015

Reprod Biol Endocrinol

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BackgroundOffspring of women with diabetes mellitus (DM) during pregnancy have a risk of developing metabolic disease in adulthood greater than that conferred by genetics alone. The mechanisms responsible are unknown, but likely involve fetal exposure to the in utero milieu, including glucose and circulating adipokines. The purpose of this study was to assess the impact of maternal DM on fetal adipokines and anthropometry in infants of Hispanic and Native American women.MethodsWe conducted a prospective study of offspring of mothers with normoglycemia (Con-O; n = 79) or type 2 or gestational DM (DM-O; n = 45) pregnancies. Infant anthropometrics were measured at birth and 1-month of age. Cord leptin, high-molecular-weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF) and C-peptide were measured by ELISA. Differences between groups were assessed using the Generalized Linear Model framework. Correlations were calculated as standardized regression coefficients and adjusted for significant covariates.ResultsDM-O were heavier at birth than Con-O (3.7 ± 0.6 vs. 3.4 ± 0.4 kg, p = 0.024), but sum of skinfolds (SSF) were not different. At 1-month, there was no difference in weight, SSF or % body fat or postnatal growth between groups. Leptin was higher in DM-O (20.1 ± 14.9 vs. 9.5 ± 9.9 ng/ml in Con-O, p < 0.0001). Leptin was positively associated with birth weight (p = 0.0007) and SSF (p = 0.002) in Con-O and with maternal hemoglobin A1c in both groups (Con-O, p = 0.023; DM-O, p = 0.006). PEDF was positively associated with birth weight in all infants (p = 0.004). Leptin was positively associated with PEDF in both groups, with a stronger correlation in DM-O (p = 0.009). At 1-month, HMWA was positively associated with body weight (p = 0.004), SSF (p = 0.025) and % body fat (p = 0.004) across the cohort.ConclusionsMaternal DM results in fetal hyperleptinemia independent of adiposity. HMWA appears to influence postnatal growth. Thus, in utero exposure to DM imparts hormonal differences on infants even without aberrant growth.

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“…Interestingly, circulating levels of PEDF demonstrate opposite changes. Several groups including us have reported that serum PEDF levels are significantly increased in patients with T1DM [81, 82] and T2DM [83, 84]. The elevated PEDF levels are positively associated with body mass index, lipid levels and vascular dysfunction [83].…”

Section: The Mechanism Underlying Abnormal Angiogenesis In Diabetesmentioning

confidence: 99%

“…Several groups including us have reported that serum PEDF levels are significantly increased in patients with T1DM [81, 82] and T2DM [83, 84]. The elevated PEDF levels are positively associated with body mass index, lipid levels and vascular dysfunction [83]. The elevated serum levels of PEDF are also found in patients with obesity [85] and metabolic syndrome [86] and in T2DM animal models [40, 87].…”

Section: The Mechanism Underlying Abnormal Angiogenesis In Diabetesmentioning

confidence: 99%

Angiogenesis in diabetes and obesity

Cheng

Xing

2015

Rev Endocr Metab Disord

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100

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The prevalence of diabetes mellitus and obesity continues to increase globally. Diabetic vascular complications are the main chronic diabetic complications and associated with mortality and disability. Angiogenesis is a key pathological characteristic of diabetic microvascular complications. However, there are two tissue-specific paradoxical changes in the angiogenesis in diabetic microvascular complications: an excessive uncontrolled formation of premature blood vessels in some tissues, such as the retina, and a deficiency in the formation of small blood vessels in peripheral tissues, such as the skin. This review will discuss the paradoxical phenomena of angiogenesis and its underlying mechanism in obesity, diabetes and diabetic complications.

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Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients

Cited by 20 publications

References 49 publications

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus

Angiogenesis in diabetes and obesity

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