Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism.

Macrophages play key roles in obesity-associated pathophysiology, including inflammation, atherosclerosis, and cancer, and processes that affect the survival-death balance of macrophages may have an important impact on obesity-related diseases. Adipocytes and other cells secrete a protein called extracellular nicotinamide phosphoribosyltransferase (eNampt; also known as pre-B cell colony enhancing factor or visfatin), and plasma levels of eNampt increase in obesity. Herein we tested the hypothesis that eNampt could promote cell survival in macrophages subjected to endoplasmic reticulum (ER) stress, a process associated with obesity and obesity-associated diseases.

Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate.

Neurogenin 3 is essential for enteroendocrine cell development; however, it is unknown whether this transcription factor is sufficient to induce an endocrine program in the intestine or how it affects the development of other epithelial cells originating from common progenitors. In this study, the mouse villin promoter was used to drive Neurogenin 3 expression throughout the developing epithelium to measure the affect on cell fate. Although the general morphology of the intestine was unchanged, transgenic founder embryos displayed increased numbers of cells expressing the pan-endocrine marker chromogranin A.

Parietal cell hyperstimulation and autoimmune gastritis in cholera toxin transgenic mice.

The stimulation of gastric acid secretion from parietal cells involves both intracellular calcium and cAMP signaling. To understand the effect of increased cAMP on parietal cell function, we engineered transgenic mice expressing cholera toxin (Ctox), an irreversible stimulator of adenylate cyclase. The parietal cell-specific H(+),K(+)-ATPase beta-subunit promoter was used to drive expression of the cholera toxin A1 subunit (CtoxA1).

Gene expression profiling of gastrin target genes in parietal cells.

Previous studies demonstrated that mice with a null mutation in the gene encoding the hormone gastrin have impaired gastric acid secretion. Hence, the aim of this study was to evaluate changes in the acid-secreting parietal cell in gastrin-deficient (GAS-KO) mice. Analysis of several transcripts encoding parietal cell proteins involved in gastric acid secretion showed reduced abundance in the GAS-KO stomach, including H+,K+-ATPase alpha- and beta-subunits, KCNQ1 potassium channel, aquaporin-4 water channel, and creatine kinase B, which were reversed by gastrin infusion for 1 wk.

Enteroendocrine cell expression of a cholecystokinin gene construct in transgenic mice and cultured cells.

CCK is predominantly expressed in subsets of endocrine cells in the intestine and neurons in the brain. We evaluated the expression of a CCK gene construct in transgenic mice and cultured cells to identify a genomic region that directs correct tissue- and cell-specific expression in enteroendocrine cells. The CCKL1 transgene contained 6.