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Author

Min Pi

Bio: Min Pi is an academic researcher from University of Tennessee Health Science Center. The author has contributed to research in topics: GPRC6A & Osteocalcin. The author has an hindex of 26, co-authored 45 publications receiving 3161 citations. Previous affiliations of Min Pi include Duke University & University of Kansas.
Topics: GPRC6A, Osteocalcin, Receptor, Osteoblast, Insulin

Papers
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Journal ArticleDOI
TL;DR: Data suggest that 1,25(OH)(2)D(3) is an important regulator of FGF23 production by osteoblasts in bone and may be to act as a counterregulatory phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.
Abstract: The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 +/- 8.1 to 213.8 +/- 14.6 pg/ml at 8 h (mean +/- SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH)(2)D(3) further increased circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH)(2)D(3) levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25(OH)(2)D(3). In osteoblast cell cultures, 1,25(OH)(2)D(3) but not calcium, phosphate, or parathyroid hormone stimulated FGF23 mRNA levels and resulted in a dose-dependent increase in FGF23 promoter activity. Overexpression of a dominant negative vitamin D receptor inhibited 1,25(OH)(2)D(3) stimulation of FGF23 promoter activity, and mutagenesis of the FGF23 promoter identified a vitamin D-responsive element (-1180 GGAACTcagTAACCT -1156) that is responsible for the vitamin D effects. These data suggest that 1,25(OH)(2)D(3) is an important regulator of FGF23 production by osteoblasts in bone. The physiologic role of FGF23 may be to act as a counterregulatory phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.

617 citations

Journal ArticleDOI
TL;DR: Reverse transcription-PCR analyses showed that mouse GPRC6A is widely expressed in mouse tissues, including bone, calvaria, and the osteoblastic cell line MC3T3-E1, and suggest that in addition to sensing amino acids, G PRC 6A is a cation-, calcimimetic-, and osteocalcin-sensing receptor and a candidate for mediating extracellular calcium-sensed responses in osteoblasts and possibly other

290 citations

Journal ArticleDOI
03 Dec 2008-PLOS ONE
TL;DR: The overall function of GPRC6A may be to coordinate the anabolic responses of multiple tissues through the sensing of extracellular amino acids, osteocalcin and divalent cations.
Abstract: Background GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown.

229 citations

Journal ArticleDOI
TL;DR: It is found that GPRC6A is a candidate for mediating the response to Ocn in the bone‐pancreas endocrine loop regulating insulin signaling, and intraperitoneal injection of Ocn stimulated ERK activity in the pancreas and increased serum insulin levels in wild‐type mice, but these responses were markedly attenuated in Gprc6a−/− mice.
Abstract: A bone-pancreas endocrine loop has been identified recently that involves insulin secreted from β-cells in the pancreas stimulating insulin receptors in osteoblasts, leading to osteoblastic differentiation and increased secretion of osteocalcin (Ocn), a bone-derived hormone that regulates insulin secretion in β-cells. The identity of the Ocn-sensing receptor in β-cells is a missing component of this endocrine loop. The abnormalities in glucose homeostasis in Gprc6a null mice suggests that this pertussis toxin–sensitive G protein–coupled receptor is a candidate for mediating the effects of Ocn on insulin secretion in the pancreas. In support of this possibility, we found that transfection of non-Gprc6a-expressing HEK-293 cells with a full-length Gprc6a cDNA imparted a dose-dependent response to Ocn (5 to 60 ng/mL), as measured by PKD1 and ERK phosphorylation. In addition, Gprc6a is highly expressed in mouse pancreatic tissue and in the mouse TC-6 pancreatic β-cell line. Ocn also stimulated ERK activity in TC-6 pancreatic β-cells. Finally, intraperitoneal injection of Ocn stimulated ERK activity in the pancreas and increased serum insulin levels in wild-type mice, but these responses were markedly attenuated in Gprc6a−/− mice. These findings suggest that GPRC6A is a candidate for mediating the response to Ocn in the bone-pancreas endocrine loop regulating insulin signaling. © 2011 American Society for Bone and Mineral Research.

204 citations

Journal ArticleDOI
TL;DR: Using size-fractionated subsets of cDNA from the first finger stage, two sets of gridded libraries were constructed for cDNA sequencing and the ESTs represent approximately 40% of genes expressed in late development, assuming that the non-redundant ESTs correspond to independent genes.
Abstract: In an effort to identify and characterize genes expressed during multicellular development in Dictyostelium, we have undertaken a cDNA sequencing project. Using size-fractionated subsets of cDNA from the first finger stage, two sets of gridded libraries were constructed for cDNA sequencing. One, li- brary S, consisting of 9984 clones, carries relatively short inserts, and the other, library L, which consists of 8448 clones, has longer inserts. We sequenced all the selected clones in library S from their 3'-ends, and this generated 3093 non-redundant, expressed sequence tags (ESTs). Among them, 246 ESTs hit known Dictyostelium genes and 910 showed significant similarity to genes of Dictyostelium and other or- ganisms. For library L, 1132 clones were randomly sequenced and 471 non-redundant ESTs were obtained. In combination, the ESTs from the two libraries represent approximately 40% of genes expressed in late development, assuming that the non-redundant ESTs correspond to independent genes. They will pro- vide a useful resource for investigating the genetic networks that regulate multicellular development of this

167 citations


Cited by
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01 Mar 2017
TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR-signaling network contributes to human disease is highlighted.
Abstract: The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.

2,014 citations

Journal ArticleDOI
TL;DR: This review provides an objective and comprehensive account of the cellular uptake of NPs and the underlying parameters controlling the nano-cellular interactions, along with the available analytical techniques to follow and track these processes.
Abstract: Nanoscale materials are increasingly found in consumer goods, electronics, and pharmaceuticals. While these particles interact with the body in myriad ways, their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. Nanoparticles (NPs) can modulate cell fate, induce or prevent mutations, initiate cell–cell communication, and modulate cell structure in a manner dictated largely by phenomena at the nano–bio interface. Recent advances in chemical synthesis have yielded new nanoscale materials with precisely defined biochemical features, and emerging analytical techniques have shed light on nuanced and context-dependent nano-bio interactions within cells. In this review, we provide an objective and comprehensive account of our current understanding of the cellular uptake of NPs and the underlying parameters controlling the nano-cellular interactions, along with the available analytical techniques to follow and track these processes.

1,498 citations

Journal ArticleDOI
TL;DR: The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca( o)(2+) on tissues that maintain systemic Ca(o](2+) homeostasis, especially parathyroid chief cells and several cells in the kidney.
Abstract: The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

1,314 citations

Journal ArticleDOI
Ludwig Eichinger1, Justin A. Pachebat1, Justin A. Pachebat2, Gernot Glöckner, Marie-Adèle Rajandream3, Richard Sucgang4, Matthew Berriman3, J. Song4, Rolf Olsen5, Karol Szafranski, Qikai Xu4, Budi Tunggal1, Sarah K. Kummerfeld2, Martin Madera2, Bernard Anri Konfortov2, Francisco Rivero1, Alan T. Bankier2, Rüdiger Lehmann, N. Hamlin3, Robert L. Davies3, Pascale Gaudet6, Petra Fey6, Karen E Pilcher6, Guokai Chen4, David L. Saunders3, Erica Sodergren4, P. Davis3, Arnaud Kerhornou3, X. Nie4, Neil Hall3, Christophe Anjard5, Lisa Hemphill4, Nathalie Bason3, Patrick Farbrother1, Brian A. Desany4, Eric M. Just6, Takahiro Morio7, René Rost8, Carol Churcher3, J. Cooper3, Stephen F. Haydock9, N. van Driessche4, Ann Cronin3, Ian Goodhead3, Donna M. Muzny4, T. Mourier3, Arnab Pain3, Mingyang Lu4, D. Harper3, R. Lindsay4, Heidi Hauser3, Kylie R. James3, M. Quiles4, M. Madan Babu2, Tsuneyuki Saito10, Carmen Buchrieser11, A. Wardroper12, A. Wardroper2, Marius Felder, M. Thangavelu, D. Johnson3, Andrew J Knights3, H. Loulseged4, Karen Mungall3, Karen Oliver3, Claire Price3, Michael A. Quail3, Hideko Urushihara7, Judith Hernandez4, Ester Rabbinowitsch3, David Steffen4, Mandy Sanders3, Jun Ma4, Yuji Kohara13, Sarah Sharp3, Mark Simmonds3, S. Spiegler3, Adrian Tivey3, Sumio Sugano14, Brian White3, Danielle Walker3, John Woodward3, Thomas Winckler, Yoshiaki Tanaka7, Gad Shaulsky4, Michael Schleicher8, George M. Weinstock4, André Rosenthal, Edward C. Cox15, Rex L. Chisholm6, Richard A. Gibbs4, William F. Loomis5, Matthias Platzer, Robert R. Kay2, Jeffrey G. Williams16, Paul H. Dear2, Angelika A. Noegel1, Bart Barrell3, Adam Kuspa4 
05 May 2005-Nature
TL;DR: A proteome-based phylogeny shows that the amoebozoa diverged from the animal–fungal lineage after the plant–animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
Abstract: The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

1,289 citations