Adipsin Is an Adipokine that Improves β Cell Function in Diabetes

Lo, James C.; Ljubicic, Sanda; Leibiger, Barbara; Kern, Matthias; Leibiger, Ingo B.; Moede, Tilo; Kelly, Molly E.; Bhowmick, Diti Chatterjee; Murano, Incoronata; Cohen, Paul; Banks, Alexander S.; Khandekar, Melin J.; Dietrich, Arne; Flier, Jeffrey S.; Cinti, Saverio; Blüher, Matthias; Danial, Nika N.; Berggren, Per Olof; Spiegelman, Bruce M.

doi:10.1016/j.cell.2014.06.005

Cited by 318 publications

(374 citation statements)

References 63 publications

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“…Previous studies, however, did not demonstrate any relation to CVD outcomes 10, 21. Adipsin has been shown to regulate inflammation in adipose tissue and may improve beta‐cell function in diabetes mellitus 11, 23, 24. Among women, adipsin is correlated with metabolic parameters, including body mass index, insulin resistance, and carotid atherosclerosis,3, 12, 25 but it has not been linked to adverse CVD outcomes previously.…”

Section: Discussionmentioning

confidence: 97%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

221

228

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BackgroundThe discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk‐stratification methods and may be informative regarding biological pathways contributing to disease.Methods and ResultsWe used a discovery proteomic platform that targeted high‐value proteins for CVD to ascertain 85 circulating protein biomarkers in 3523 Framingham Heart Study participants (mean age, 62 years; 53% women). Using multivariable‐adjusted Cox models to account for clinical variables, we found 8 biomarkers associated with incident atherosclerotic CVD, 18 with incident heart failure, 38 with all‐cause mortality, and 35 with CVD death (false discovery rate, q<0.05 for all; P‐value ranges, 9.8×10−34 to 3.6×10−2). Notably, a number of regulators of metabolic and adipocyte homeostasis were associated with cardiovascular events, including insulin‐like growth factor 1 (IGF1), insulin‐like growth factor binding protein 1 (IGFBP1), insulin‐like growth factor binding protein 2 (IGFBP2), leptin, and adipsin. In a multimarker approach that accounted for clinical factors, growth differentiation factor 15 (GDF15) was associated with all outcomes. In addition, N‐terminal pro‐b‐type natriuretic peptide, C‐reactive protein, and leptin were associated with incident heart failure, and C‐type lectin domain family 3 member B (CLEC3B; tetranectin), N‐terminal pro‐b‐type natriuretic peptide, arabinogalactan protein 1 (AGP1), soluble receptor for advanced glycation end products (sRAGE), peripheral myelin protein 2 (PMP2), uncarboxylated matrix Gla protein (UCMGP), kallikrein B1 (KLKB1), IGFBP2, IGF1, leptin receptor, and cystatin‐C were associated with all‐cause mortality in a multimarker model.ConclusionsWe identified numerous protein biomarkers that predicted cardiovascular outcomes and all‐cause mortality, including biomarkers representing regulators of metabolic homeostasis and inflammatory pathways. Further studies are needed to validate our findings and define clinical utility, with the ultimate goal of improving strategies for CVD prevention.

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Section: Discussionmentioning

confidence: 97%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

221

228

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“…Most recently, experimental and clinical studies suggest that novel adipokines such as adipsin and visfatin might have an energetic role in the cascade of the events leading to diabetes mellitus. Namely, adipsin has a beneficial role in maintaining β cell function and visfatin plays an important role in glucose metabolism (2,3).…”

Section: Introductionmentioning

confidence: 99%

Reciprocal changes of serum adispin and visfatin levels in patients with type 2 diabetes after an overnight fast

Legakis

Mantzouridis²,

Bouboulis

et al. 2016

Arch. Endocrinol. Metab.

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Objective: In order to elucidate the interrelationship of adipokines in glucose hemiostasis, we determined the concentration of visfatin and adipsin in blood samples in patients with type 2 diabetes and age-matched controls after an overnight fast. Subjects and methods: We enrolled 37 patients with known type 2 diabetes -21 males and 16 females, aged 62.95 ± 15.72 years and 43 controls-28 males and 15 females, aged 60.79 ± 12.67 years. Blood samples were collected after an overnight fast and routine biochemical parameters such as glucose, cholesterol, HDL, LDL, triglycerides along with Hb1Ac, insulin and c-peptide, in addition to circulating visfatin and adipsin were determined in all samples. Data were considered significant at a level of p < 0.05. Results: In patients with type 2 diabetes, circulating adipsin levels were decreased and inversely related with glucose levels while circulating visfatin was increased significantly in the fasting state. Conclusion: These results implicate the adipokines adipsin and visfatin as possible participants in the pathogenesis of type 2 diabetes.Arch Endocrinol Metab. 2016;60(1):76-8

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“…In adipsin -/-mice, Lo et al showed that this protein plays an important role in insulin secretion by the pancreatic β-cells. They also showed that adipsin is decreased in patients with T2D and β-cell failure [110]. The data by Lo et al suggest that adipsin stimulates insulin secretion via actions of C3a on its receptor to improve glucose homeostasis in vivo.…”

Section: Further Adipokinesmentioning

confidence: 80%

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Schleinitz¹

2016

Rev Diabet Stud

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■ AbstractAdipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the "protective" allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed.

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Adipsin Is an Adipokine that Improves β Cell Function in Diabetes

Cited by 318 publications

References 63 publications

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Reciprocal changes of serum adispin and visfatin levels in patients with type 2 diabetes after an overnight fast

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

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