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Publication
Dual CCR2/CCR5 antagonist treatment attenuates adipose inflammation, but not
microvascular complications in ob/ob mice.
Authors O'Brien PD, Hinder LM, Parlee SD, Hayes JM, Backus C, Zhang H, Ma L, Sakowski
SA, Brosius FC, Feldman EL
Submitted By Eva Feldman on 6/5/2017
Status Published
Journal Diabetes, obesity & metabolism
Year 2017
Date Published
Volume : Pages Not Specified : Not Specified
PubMed Reference 28332276
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.






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Lepleptin

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