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).

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.

§ 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

 
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