TITLE

Vaspin inhibits kallikrein 7 by serpin mechanism

AUTHOR(S)
Heiker, John; Klöting, Nora; Kovacs, Peter; Kuettner, E.; Sträter, Norbert; Schultz, Stephan; Kern, Matthias; Stumvoll, Michael; Blüher, Matthias; Beck-Sickinger, Annette
PUB. DATE
July 2013
SOURCE
Cellular & Molecular Life Sciences;Jul2013, Vol. 70 Issue 14, p2569
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin-hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.
ACCESSION #
88349403

 

Related Articles

  • Chronic Olanzapine Treatment Induces Disorders of Plasma Fatty Acid Profile in Balb/c Mice: A Potential Mechanism for Olanzapine-Induced Insulin Resistance. Li, Huqun; Fang, Maosheng; Xu, Mingzhen; Li, Shihong; Du, Juan; Li, Weiyong; Chen, Hui // PLoS ONE;12/14/2016, Vol. 11 Issue 12, p1 

    Background: Atypical antipsychotics such as olanzapine cause metabolic side effects leading to obesity and insulin resistance. The underlying mechanisms remain elusive. In this study we investigated the effects of chronic treatment of olanzapine on the fatty acid composition of plasma in mice....

  • Increased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice. Pang, Jingbo; Rhodes, Davina H.; Pini, Maria; Akasheh, Rand T.; Castellanos, Karla J.; Cabay, Robert J.; Cooper, Dianne; Perretti, Mauro; Fantuzzi, Giamila // PLoS ONE;Feb2013, Vol. 8 Issue 2, p1 

    Obesity and type 2 diabetes are associated with increased production of Galectin-3 (Gal-3), a protein that modulates inflammation and clearance of glucose adducts. We used Lean and Diet-induced Obese (DIO) WT and Gal-3 KO mice to investigate the role of Gal-3 in modulation of adiposity, glucose...

  • Decreased Insulin Clearance in Individuals with Elevated 1-h Post-Load Plasma Glucose Levels. Marini, Maria Adelaide; Frontoni, Simona; Succurro, Elena; Arturi, Franco; Fiorentino, Teresa Vanessa; Sciacqua, Angela; Hribal, Marta Letizia; Perticone, Francesco; Sesti, Giorgio // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥8.6 mmol/l (155 mg/dl) at 1 h during an oral glucose tolerance test (OGTT) can identify individuals at high risk for type 2 diabetes...

  • Serum Visfatin Levels, Adiposity and Glucose Metabolism in Obese Adolescents. Taşkesen, Derya; Kirel, Birgül; Us, Tercan // Journal of Clinical Research in Pediatric Endocrinology;Jun2012, Vol. 4 Issue 2, p76 

    Objective: Visfatin, an adipokine, has insulin-mimetic effects. The main determinants of both the production and the physiologic role of visfatin are still unclear. The aim of this study is to determine the relation of serum visfatin to adiposity and glucose metabolism. Methods: 40 pubertal...

  • Dietary Advanced Glycation End Products Consumption as a Direct Modulator of Insulin Sensitivity in Overweight Humans: A Study Protocol for a Double-Blind, Randomized, Two Period Cross-Over Trial. de Courten, Barbora; de Courten, Maximilian P. J.; Schalkwijk, Casper G.; Walker, Karen Z.; Forbes, Josephine // Journal of Medical Internet Research;Jul2015, Vol. 17 Issue 7, p1 

    Background: Advanced glycation end products (AGEs) are formed during the processing, storage, and cooking of foods. As part of a western diet, AGEs are consumed in excess and impair glucose metabolism in patients with type 2 diabetes. In the absence of diabetes, AGE-mediated decreases in insulin...

  • SERUM VISFATIN IN RELATION TO SOME PARAMETERS OF IRON METABOLISM IN EGYPTIAN SUBJECTS WITH ALTERED GLUCOSE TOLERANCE. Abdullah, Nadia M.; Gadallah, Fadila A.; Hamid, Fatma F. Abdel; El-Moneam, Tahany M. Abd; El-Baki, Rania S. Abd; Ibrahim, Doaa M. // Egyptian Journal of Biochemistry & Molecular Biology;Dec2012, Vol. 30 Issue 2, p137 

    Visfatin is an adipokine mainly synthesized and secreted in visceral fat. Visfatin was found to have important proinflammatory and immunomodulating properties. The aim of the present work was to clarify the relation between plasma visfatin, some parameters of iron metabolism and insulin...

  • Glypican-4 is increased in human subjects with impaired glucose tolerance and decreased in patients with newly diagnosed type 2 diabetes. Li, Ke; Xu, Xiaohui; Hu, Wenjing; Li, Minyan; Yang, Mengliu; Wang, Yaxu; Luo, Yong; Zhang, Xianxiang; Liu, Hua; Li, Ling; Yang, Gangyi // Acta Diabetologica;Dec2014, Vol. 51 Issue 6, p981 

    Context: Glypican-4 (GPC-4) has been identified as a novel adipokine capable of enhancing insulin signaling. A significant association between circulating GPC-4 levels and nonalcoholic fatty liver disease and cardiometabolic risk factors has been found in women. Objective: The aim of the present...

  • Erratum.  // Diabetes Care;Jul2014, Vol. 37 Issue 7, p2063 

    A correction to the article "A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test" that was published in a 2001 issue is presented.

  • Adipokines and central control in adenosine A1 receptor dependent glucose metabolism. Faulhaber-Walter, Robert // Adipocyte;Apr-Jun2012, Vol. 1 Issue 2, p108 

    Adenosine A1 receptor-deficient mice develop a phenotype of insulin resistance and grow fat. Participating pathophysiological pathways are not understood in detail yet, as discussed in our recent manuscript. This commentary further explores possible pathophysiological mechanisms with emphasis on...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics