Neuropeptide stimulation caused an up-regulation of neuropeptide receptor expression
in keratinocytes and a dramatic increase in keratinocyte secretion of SP and CGRP, suggesting possible autocrine or paracrine stimulatory effects and amplification of neuropeptide signaling. Both SP and CGRP concentration-dependently stimulated cellular proliferation and the expression and secretion of inflammatory cytokines and NGF in keratinocytes. SP also activated all 3 families of mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NF kappa B) in keratinocytes, while CGRP only activated p38 and extracellular signal CP-690550 clinical trial related kinase1/2 (ERK1/2) MAPKs. Neuropeptide stimulated inflammatory mediatory production in keratinocytes was reversed by ERK1/2 and INK inhibitors. The current study is the first to observe; 1) that CGRP stimulates keratinocyte expression of CGRP and its receptor complex, 2) that SP and CGRP stimulate IL-6 and
TNF-alpha secretion in keratinocytes, 3) that SP activated all three MAPK families and the NF kappa B transcriptional signaling see more pathway in keratinocytes, and 4) that SP and CGRP stimulated inflammatory mediator production in keratinocytes is dependent on ERK1/2 and JNK activation. These studies provide evidence suggesting that disruption of ERK1/2 and JNK signaling may potentially be an effective therapy for inflammatory skin diseases and pain syndromes mediated by exaggerated sensory neuronkeratinocyte signaling. Published by Elsevier B.V.”
“The potential reversibility of a reduced incretin effect is unclear. We investigated the incretin
effect during third trimester and 3 to 4 months postpartum selleck compound in women with and without gestational diabetes mellitus (GDM). Ten women with GDM (plasma glucose (PG) concentration at 120 min after 75 g-oral glucose tolerance test (OGTT) (PG(120min)): 10.1 +/- 0.6 mmol/l (mean +/- SEM)) and eight women with normal glucose tolerance (NGT; PG(120min): 7.0 +/- 0.1 mmol/l) were investigated on four occasions: 4 h 50 g-OGTT and isoglycaemic intravenous glucose infusion during third trimester and 3 to 4 months postpartum. In women with GDM, the incretin effect increased significantly postpartum (31 +/- 6 vs. 56 +/- 6%, p = 0.02), whereas the increment in women with NGT was insignificant (35 +/- 12 vs. 56 +/- 9%, p = 0.08). Similarly, the gastrointestinal-mediated glucose disposal (GIGD = 100% x (glucose(OGTT) – glucose(IIGI))/glucose(OGTT)) was reduced to diabetic levels in women with GDM (37 +/- 3%), but increased (p = 0.030) to normal levels post partum (58 +/- 6%). GIGD did not change significantly in NGT women (48 +/- 3 vs. 57 +/- 6%, p = 0.94).