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Modified UCN2 Pepti...
Modified UCN2 Peptide Acts as an Insulin Sensitizer in Skeletal Muscle of Obese Mice
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Borg, ML (author)
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Massart, J (author)
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Schonke, M (author)
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- Barbosa, TD (author)
- Karolinska Institutet
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Guo, LL (author)
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Wade, M (author)
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Alsina-Fernandez, J (author)
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Miles, R (author)
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Ryan, A (author)
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Bauer, S (author)
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Coskun, T (author)
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O'Farrell, E (author)
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Niemeier, EM (author)
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- Chibalin, AV (author)
- Karolinska Institutet
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- Krook, A (author)
- Karolinska Institutet
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- Karlsson, HK (author)
- Karolinska Institutet
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Brozinick, JT (author)
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- Zierath, JR (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2019-04-22
- 2019
- English.
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:7, s. 1403-1414
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https://diabetes.dia...
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http://kipublication...
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https://doi.org/10.2...
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Abstract
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- The neuropeptide urocortin 2 (UCN2) and its receptor corticotropin-releasing hormone receptor 2 (CRHR2) are highly expressed in skeletal muscle and play a role in regulating energy balance and glucose metabolism. We investigated a modified UCN2 peptide as a potential therapeutic agent for the treatment of obesity and insulin resistance, with a specific focus on skeletal muscle. High-fat–fed mice (C57BL/6J) were injected daily with a PEGylated UCN2 peptide (compound A) at 0.3 mg/kg subcutaneously for 14 days. Compound A reduced body weight, food intake, whole-body fat mass, and intramuscular triglycerides compared with vehicle-treated controls. Furthermore, whole-body glucose tolerance was improved by compound A treatment, with increased insulin-stimulated Akt phosphorylation at Ser473 and Thr308 in skeletal muscle, concomitant with increased glucose transport into extensor digitorum longus and gastrocnemius muscle. Mechanistically, this is linked to a direct effect on skeletal muscle because ex vivo exposure of soleus muscle from chow-fed lean mice to compound A increased glucose transport and insulin signaling. Moreover, exposure of GLUT4-Myc–labeled L6 myoblasts to compound A increased GLUT4 trafficking. Our results demonstrate that modified UCN2 peptides may be efficacious in the treatment of type 2 diabetes by acting as an insulin sensitizer in skeletal muscle.
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- art (subject category)
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Diabetes
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- By the author/editor
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Borg, ML
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Massart, J
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Schonke, M
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Barbosa, TD
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Guo, LL
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Wade, M
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show more...
-
Alsina-Fernandez ...
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Miles, R
-
Ryan, A
-
Bauer, S
-
Coskun, T
-
O'Farrell, E
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Niemeier, EM
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Chibalin, AV
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Krook, A
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Karlsson, HK
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Brozinick, JT
-
Zierath, JR
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show less...
- Articles in the publication
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Diabetes
- By the university
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Karolinska Institutet