Elevated plasma pigment epithelium-derived factor in children with type 2 diabetes mellitus is attributable to obesity

Tryggestad, Jeanie B.; Wang, Joshua J.; Zhang, Sarah X.; Thompson, David M.; Short, Kevin R.

doi:10.1111/pedi.12226

Cited by 14 publications

(9 citation statements)

References 20 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: 60%

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: 60%

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Hudson

Dancho

et al. 2016

Mol Med

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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%

“…Adipose tissues also generate endogenous angiogenic inhibitors [77, 154]. PEDF, angiostatin, endostatin, and TSP-1 are increased in overweight/obese subjects or animal models of obesity [40, 84–87, 155]. There is no difference in adipose tissue development between TSP-1 deficient mice and control wild-type mice after high-calorie diet feed [156].…”

Section: Angiogenesis In Adipose Tissue Of Obesitymentioning

confidence: 99%

Angiogenesis in diabetes and obesity

Cheng

Xing

2015

Rev Endocr Metab Disord

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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“…While PEDF is associated with insulin resistance in adults [16], limited data are available in children [17]. Tryggestad et al reported that PEDF concentrations were similar in obese children with and without type 2 diabetes and were higher in obese compared to normal weight children, regardless of diabetes [17].…”

Section: Introductionmentioning

confidence: 99%

Pigment Epithelium-Derived Factor Declines in Response to an Oral Glucose Load and Is Correlated with Vitamin D and BMI but Not Diabetes Status in Children and Young Adults

et al. 2017

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Background: Pigment epithelium-derived factor (PEDF) is associated with obesity and diabetes complications in adults, yet little is known about PEDF in younger individuals. We investigated the relationship between PEDF and various metabolic biomarkers in young healthy volunteers (HV) and similar-aged patients with diabetes (type 1 and type 2). Methods: A fasting blood sample was collected in 48 HV, 11 patients with type 1 diabetes (T1D), and 11 patients with type 2 diabetes (T2D) 12–25 years of age. In 9 healthy subjects, PEDF was also serially measured during a frequently sampled oral glucose tolerance test (OGTT). Results: PEDF was positively correlated with BMI and systolic blood pressure and negatively correlated with vitamin D. Upon multivariable analysis, BMI and vitamin D were independent predictors of PEDF. Prior to adjustment, PEDF was highest in T2D patients (7,168.9 ± 4417.4 ng/mL) and lowest in individuals with T1D (2,967.7 ± 947.1 ng/mL) but did not differ by diagnosis when adjusted for BMI and vitamin D. Among volunteers who underwent an OGTT, PEDF declined by ∼20% in response to an oral glucose load. Conclusion: PEDF was acutely regulated by a glucose load and was correlated with BMI but not with diabetes. The negative correlation with vitamin D, independent of BMI, raises the question whether PEDF plays a compensatory role in bone matrix mineralization.

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Elevated plasma pigment epithelium-derived factor in children with type 2 diabetes mellitus is attributable to obesity

Cited by 14 publications

References 20 publications

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

Angiogenesis in diabetes and obesity

Pigment Epithelium-Derived Factor Declines in Response to an Oral Glucose Load and Is Correlated with Vitamin D and BMI but Not Diabetes Status in Children and Young Adults

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