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Horm Metab Res 2020; 52(09): 685-688
DOI: 10.1055/a-1126-4402
Endocrine Research

COMP-Ang-1 Improves Glucose Uptake in db/db Mice with Type 2 Diabetes

Petra Baum‡
1   Department of Neurology, University of Leipzig, Leipzig, Germany
,
Sabine Paeschke‡
2   Institute of Anatomy, University of Leipzig, Leipzig, Germany
,
Nora Klöting
3   Department of Medicine, University of Leipzig, Leipzig, Germany
4   Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Leipzig, Germany
,
Matthias Blüher
3   Department of Medicine, University of Leipzig, Leipzig, Germany
,
Matthias Kern
3   Department of Medicine, University of Leipzig, Leipzig, Germany
,
Heike Serke
5   CBTM, Anatomy and Developmental Biology, University of Heidelberg, Mannheim, Germany
,
Marcin Nowicki   §
2   Institute of Anatomy, University of Leipzig, Leipzig, Germany
,
Joanna Kosacka   §
1   Department of Neurology, University of Leipzig, Leipzig, Germany
3   Department of Medicine, University of Leipzig, Leipzig, Germany
› Author Affiliations Funding: This study was supported by Deutsche Diabetes-Stiftung, 368/03/15, 93400–989 (to JK) and SFB1052/2 B04 (to NK).
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Abstract

Cartilage oligomeric matrix protein (COMP)-Angiopoietin-1 is a potent angiopoietin-1 (Ang-1) variant that possesses therapeutic potential in angiogenesis and vascular endothelial dysfunction. Noteworthy, we have shown that COMP-Ang-1 improves hyperglycemia and neuroregeneration in ob/ob mice. However, the mechanism of the antidiabetic effect of COMP-Ang-1 is completely unknown. Therefore, we elucidated the diabetes protective molecular mechanisms of COMP-Ang-1 in diabetic db/db mouse model. COMP-Ang-1 (0.5 ng/g body weight) or aqueous NaCl solution was injected intraperitoneally per day in 21 consecutive days into 3-month old, male db/db mice (n=10 per group). Blood glucose and HbA1c levels were determined at baseline and 21 days after COMP-Ang-1 or NaCl treatment. The effect of COMP-Ang-1 on glucose uptake was investigated by euglycemic-hyperinsulinemic clamp studies and key genes of glucose metabolism were studied by Western blot analysis. Our findings indicate that COMP-Ang-1 improves glucose metabolism in a tissue specific manner by regulating HIF-1α transcriptional genes of GLUT-1 expression.

Key words

COMP-Ang-1 - HIF-1α glucose uptake - type 2 diabetes - db/db mice

§ Equal co-senior authors




Publication History

Received: 27 November 2019

Accepted: 18 February 2020

Article published online:
06 April 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Jain RK. Molecular regulation of vessel maturation. Nat Med 2003; 9: 685-693
    CrossrefPubMedSearch in Google Scholar
  • 2 Cho CH, Kammerer RA, Lee HJ. et al. Designed angiopoietin-1 variant, COMP-Ang-1, protects against radiation-induced endothelial cell apoptosis. Proc Natl Acad Sci USA 2004; 101: 5553-5558
    CrossrefPubMedSearch in Google Scholar
  • 3 Kosacka J, Nowicki M, Klöting N. et al. COMP-angiopoietin-1 recovers molecular biomarkers of neuropathy and improves vascularisation in sciatic nerve of ob/ob mice. PloS ONE 2012; 7: e32881
    CrossrefPubMedSearch in Google Scholar
  • 4 Kern M, Klöting N, Mark M. et al. The SGLT2 inhibitor empagliflozin improves insulin sensitivity in db/db mice both as monotherapy and in combination with linagliptin. Metabolism 2016; 65: 114-123
    CrossrefPubMedSearch in Google Scholar
  • 5 Lee S, Kim W, Moon SO. et al. Renoprotective effect of COMP-aniopoietin-1 in db/db mice with type 2 diabetes. Nephrol Dial Transplant 2007; 22: 396-408
    CrossrefPubMedSearch in Google Scholar
  • 6 Thorens B, Mueckler M. Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab 2010; 298: E141-E145
    CrossrefPubMedSearch in Google Scholar
  • 7 Del Guerra S, Lupi R, Marselli L. et al. Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 2005; 54: 727-735
    CrossrefPubMedSearch in Google Scholar
  • 8 Bento CF. , Pereira Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes. Diabetologia 2011; 54: 1946-1956
    CrossrefPubMedSearch in Google Scholar
  • 9 Youn SW, Lee SW, Lee J. et al. COMP-Ang1 stimulates HIF-1α-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment. Blood 2011; 117: 4376-4386
    CrossrefPubMedSearch in Google Scholar
  • 10 Varela L, Suyama S, Huang Y. et al. Endothelial HIF-1α enables hypothalamic glucose uptake to drive POMC neurons. Diabetes 2017; 66: 1511-1520
    CrossrefPubMedSearch in Google Scholar