Individual Subtypes of Enteroendocrine Cells in the Mouse Small Intestine Exhibit Unique Patterns of Inositol 1,4,5-trisphosphate Receptor Expression

Wang, Songyan; Liu, Jianfeng; Li, Lin; Wice, Burton M.

doi:10.1177/002215540405200106

Cited by 17 publications

(18 citation statements)

References 55 publications

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“…Transcripts encoding GIP were greatly reduced in the intestines from GIP/DT animals. In the mouse, chromogranin A is produced by many types of EE cells but not by those that produce GIP (42). Chromogranin A transcripts were present at similar levels along the entire proximal to distal axis of intestines from wild-type and GIP/DT animals ( Fig.…”

Section: Regulatory Elements From the Gip Promoter And Gene Confine Tmentioning

confidence: 90%

“…Immunohistochemistry-Small intestines were harvested, fixed, sectioned, and labeled using indirect immunofluorescence techniques as previously described (41,42). Rabbit polyclonal antibodies to DsRed2 were obtained from Clontech.…”

Section: Methodsmentioning

confidence: 99%

“…Some animals were injected with bromodeoxyuridine 90 min before they were sacrificed to label proliferating cells (52). To estimate the number of EE cells that co-express GLP-1 plus GIP, Swiss rolls of mouse small intestines from wild-type C57BL/6J mice were double-labeled using guinea pig anti-GIP plus rabbit anti-GLP-1 antibodies (42). The number of EE cells positive for GIP alone, GLP-1 alone, or GIP plus GLP-1 in random fields along the entire duodenal to ileal axis were then counted (42,52).…”

Section: Methodsmentioning

confidence: 99%

“…To estimate the number of EE cells that co-express GLP-1 plus GIP, Swiss rolls of mouse small intestines from wild-type C57BL/6J mice were double-labeled using guinea pig anti-GIP plus rabbit anti-GLP-1 antibodies (42). The number of EE cells positive for GIP alone, GLP-1 alone, or GIP plus GLP-1 in random fields along the entire duodenal to ileal axis were then counted (42,52). More than 100 EE cells positive for each incretin were counted in the small intestine of each mouse.…”

Section: Methodsmentioning

confidence: 99%

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Targeted Ablation of Glucose-dependent Insulinotropic Polypeptide-producing Cells in Transgenic Mice Reduces Obesity and Insulin Resistance Induced by a High Fat Diet

Althage

Ford

Wang

et al. 2008

Journal of Biological Chemistry

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163

125

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The K cell is a specific sub-type of enteroendocrine cell located in the proximal small intestine that produces glucosedependent insulinotropic polypeptide (GIP), xenin, and potentially other unknown hormones. Because GIP promotes weight gain and insulin resistance, reducing hormone release from K cells could lead to weight loss and increased insulin sensitivity. However, the consequences of coordinately reducing circulating levels of all K cell-derived hormones are unknown. To reduce the number of functioning K cells, regulatory elements from the rat GIP promoter/gene were used to express an attenuated diphtheria toxin A chain in transgenic mice. K cell number, GIP transcripts, and plasma GIP levels were profoundly reduced in the GIP/DT transgenic mice. Other enteroendocrine cell types were not ablated. Food intake, body weight, and blood glucose levels in response to insulin or intraperitoneal glucose were similar in control and GIP/DT mice fed standard chow. In contrast to single or double incretin receptor knock-out mice, the incretin response was absent in GIP/DT animals suggesting K cells produce GIP plus an additional incretin hormone. Following high fat feeding for 21-35 weeks, the incretin response was partially restored in GIP/DT mice. Transgenic versus wildtype mice demonstrated significantly reduced body weight (25%), plasma leptin levels (77%), and daily food intake (16%) plus enhanced energy expenditure (10%) and insulin sensitivity. Regardless of diet, long term glucose homeostasis was not grossly perturbed in the transgenic animals. In conclusion, studies using GIP/DT mice demonstrate an important role for K cells in the regulation of body weight and insulin sensitivity. Enteroendocrine (EE)2 cells are a complex population of rare, diffusely distributed hormone-producing intestinal epithelial cells (1-3). Peptides and hormones secreted by EE cells play important roles in many aspects of gastrointestinal and whole animal physiology (4 -6). There are at least 16 different subtypes of EE cells based upon the major product(s) synthesized and secreted by individual cells (1). Several EE cell products, including GIP, glucagon-like peptide-1 (GLP-1), ghrelin, cholecystokinin, and peptide tyrosine, regulate food intake and/or degree of adiposity (7-11).GIP is produced almost exclusively by K cells located in the proximal small intestine and is secreted immediately after ingestion of a meal (4, 5, 12, 13). GIP release is regulated by nutrients in the intestinal lumen but not by those in the blood (4,6,13,14). Glucose (12,15,16), protein hydrolysates (17), specific amino acids (18), and fat (19) are major GIP secretagogues. Long term administration of a high fat diet increases intestinal GIP mRNA and peptide levels (12), as well as the circulating amount of plasma GIP (20, 21). There is a large body of biochemical and animal data suggesting that GIP signaling promotes the accumulation of fat (22-31). Obese humans also hyper-secrete GIP (32-36) suggesting that GIP may promote obesity in humans.Originally, G...

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Section: Regulatory Elements From the Gip Promoter And Gene Confine Tmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Targeted Ablation of Glucose-dependent Insulinotropic Polypeptide-producing Cells in Transgenic Mice Reduces Obesity and Insulin Resistance Induced by a High Fat Diet

Althage

Ford

Wang

et al. 2008

Journal of Biological Chemistry

Self Cite

163

125

View full text Add to dashboard Cite

show abstract

“…5A-D). To confirm the specificity of immunolabeling for the InsP 3 R, we used an affinitypurified polyclonal InsP 3 R antibody raised against a different amino acid sequence (aa 2596 -2608 vs 2492-2502) (Table 1) of the human InsP 3 R C-terminal domain (Bourguignon et al, 1994;Wang et al, 2004). Nanogold immunocytochemistry with thisantibody revealed strong but sporadic InsP 3 R expression in dendritic spine apparata (supplemental Fig.…”

Section: Methodsmentioning

confidence: 99%

Microdomains for Dopamine Volume Neurotransmission in Primate Prefrontal Cortex

Paspalas¹

2004

Journal of Neuroscience

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The explicit yet enigmatic involvement of dopamine in cortical physiology is in part volumetric (beyond the synapse), as is apparently the action of neuroleptics targeting dopamine receptors. The notion that nonsynaptic neuronal membranes would translate extracellular dopamine into receptor-specific spatiotemporal downstream signaling, similar to the chemical synapse, is intriguing. Here, we report that dopamine D 5 (but not D 1 or D 2 ) receptors in the perisomatic plasma membrane of prefrontal cortical neurons form discrete and exclusively extrasynaptic microdomains with inositol 1,4,5-trisphosphate-gated calcium stores of subsurface cisterns and mitochondria. These findings introduce a novel dopaminoceptive substratum in the brain and a unique D 5 receptor-specific signaling paradigm.

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Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells

Bezençon

Fürholz

Raymond

et al. 2008

J of Comparative Neurology

221

228

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To determine the role in chemosensation of intestinal solitary cells that express taste receptors and Trpm5, we carried out a microarray study of the transcriptome of FACS-sorted transgenic mouse intestinal cells expressing enhanced green fluorescent protein (eGFP) under the control of the Trpm5 promoter and compared it with that of intestinal cells that do not express eGFP. The findings of the study are: 1) Morphology and expression of markers show that most eGFP+ cells are brush cells. 2) The majority of proteins known to be involved in taste signal transduction are expressed in the eGFP+ cells, although the isoforms are not always the same. 3) eGFP+ cells express pre- and postsynaptic markers and nerves are often found in close proximity. 4) Several genes that play a role in inflammation are expressed specifically in eGFP+ cells. Furthermore, these cells express the entire biosynthesis pathway of leucotriene C4, an eicosanoid involved in modulation of intestinal smooth muscle contraction. 5) Angiotensinogen, renin, and succinate receptor genes are expressed in the eGFP+ cells, suggesting a role in the regulation of water and sodium transport, vasomotricity, and blood pressure. These data suggest that the Trpm5-expressing cells integrate many signals, including chemical signals from ingested food, and that they may regulate several physiological functions of the gastrointestinal tract.

show abstract

Individual Subtypes of Enteroendocrine Cells in the Mouse Small Intestine Exhibit Unique Patterns of Inositol 1,4,5-trisphosphate Receptor Expression

Cited by 17 publications

References 55 publications

Targeted Ablation of Glucose-dependent Insulinotropic Polypeptide-producing Cells in Transgenic Mice Reduces Obesity and Insulin Resistance Induced by a High Fat Diet

Targeted Ablation of Glucose-dependent Insulinotropic Polypeptide-producing Cells in Transgenic Mice Reduces Obesity and Insulin Resistance Induced by a High Fat Diet

Microdomains for Dopamine Volume Neurotransmission in Primate Prefrontal Cortex

Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells

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