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Dual CCR2/ CCR5 antagonist treatment attenuates adipose inflammation, but not microvascular complications in ob/ob mice.
- Source :
-
Diabetes, Obesity & Metabolism . Oct2017, Vol. 19 Issue 10, p1468-1472. 1p. - Publication Year :
- 2017
-
Abstract
- Diabetic peripheral neuropathy ( DPN) and diabetic kidney disease ( DKD) are common diabetic complications with limited treatment options. Experimental studies show that targeting inflammation using chemokine receptor ( CCR) antagonists ameliorates DKD, presumably by reducing macrophage accumulation or activation. As inflammation is implicated in DPN development, we assessed whether CCR2 and CCR5 antagonism could also benefit DPN. Five-week-old ob/ob mice were fed a diet containing MK-0812, a dual CCR2-CCR5 receptor antagonist, for 8 weeks; DPN, DKD and metabolic phenotyping were then performed to determine the effect of CCR inhibition. Although MK-0812 reduced macrophage accumulation in adipose tissue, the treatment had largely no effect on metabolic parameters, nerve function or kidney disease in ob/ob mice. These results conflict with published data that demonstrate a benefit of CCR antagonists for DKD and hyperglycaemia. We conclude that CCR signaling blockade is ineffective in ob/ob mice and suspect that this is explained by the severe hyperglycaemia found in this model. It remains to be determined whether MK-0812 treatment, alone or in combination with improved glycaemic control, is useful in preventing diabetic complications in alternate animal models. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14628902
- Volume :
- 19
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Diabetes, Obesity & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 125297210
- Full Text :
- https://doi.org/10.1111/dom.12950