Diabetes
-
Diabetic patients often experience visceral hypersensitivity and anorectal dysfunction. We hypothesize that the enhanced excitability of colon projecting dorsal root ganglia (DRG) neurons observed in diabetes is caused by a decrease in the amplitude of the transient A-type K(+) (I(A)) currents resulting from increased phosphorylation of mitogen-activated protein kinases (MAPK) and reduced opening of K(v)4.2 channels. ⋯ We demonstrated that reduction of the I(A) current in STZ-D DRG neurons is triggered by impaired [Ca(2+)](i) ion homeostasis, and this in turn activates the PKC-MAPK pathways, resulting in decreased opening of the K(v)4.2 channels. Hence, the PKC-MAPK-K(v)4.2 pathways represent a potential therapeutic target for treating visceral hypersensitivity in diabetes.
-
High-fat diet (HFD)-induced adipose tissue inflammation is a critical feature of diet-induced insulin resistance (IR); however, the contribution of interleukin-1 receptor I (IL-1RI)-mediated signals to this phenotype has not been defined. We hypothesized that lack of IL-1RI may ameliorate HFD-induced IR by attenuating adipose tissue inflammation. ⋯ Lack of IL-1RI protects against HFD-induced IR coincident with reduced local adipose tissue inflammation, despite equivalent immune cell recruitment.