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Gluconeogenesis

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https://www.readbyqxmd.com/read/28342842/protectin-dx-suppresses-hepatic-gluconeogenesis-through-ampk-ho-1-mediated-inhibition-of-er-stress
#1
Tae Woo Jung, Hyung-Chun Kim, Ji Hoon Jeong
Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6...
March 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#2
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28338685/prebiotic-synthesis-of-phosphoenol-pyruvate-by-%C3%AE-phosphorylation-controlled-triose-glycolysis
#3
Adam J Coggins, Matthew W Powner
Phosphoenol pyruvate is the highest-energy phosphate found in living organisms and is one of the most versatile molecules in metabolism. Consequently, it is an essential intermediate in a wide variety of biochemical pathways, including carbon fixation, the shikimate pathway, substrate-level phosphorylation, gluconeogenesis and glycolysis. Triose glycolysis (generation of ATP from glyceraldehyde 3-phosphate via phosphoenol pyruvate) is among the most central and highly conserved pathways in metabolism. Here, we demonstrate the efficient and robust synthesis of phosphoenol pyruvate from prebiotic nucleotide precursors, glycolaldehyde and glyceraldehyde...
April 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28337802/the-snf1-activating-kinase-sak1-is-a-key-regulator-of-metabolic-adaptation-and-in-vivo-fitness-of-candida-albicans
#4
Bernardo Ramírez-Zavala, Austin Mottola, Julia Haubenreißer, Sabrina Schneider, Stefanie Allert, Sascha Brunke, Knut Ohlsen, Bernhard Hube, Joachim Morschhäuser
The metabolic flexibility of the opportunistic fungal pathogen Candida albicans is important for colonisation and infection of different host niches. Complex regulatory networks, in which protein kinases play central roles, link metabolism and other virulence-associated traits, such as filamentous growth and stress resistance, and thereby control commensalism and pathogenicity. By screening a protein kinase deletion mutant library that was generated in the present work using an improved SAT1 flipper cassette, we found that the previously uncharacterised kinase Sak1 is a key upstream activator of the protein kinase Snf1, a highly conserved regulator of nutrient stress responses that is essential for viability in C...
March 23, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28337713/the-potential-role-of-fibroblast-growth-factor-21-in-lipid-metabolism-and-hypertension
#5
REVIEW
Zhe Huang, Aimin Xu, Bernard M Y Cheung
Fibroblast growth factor (FGF) 21 belongs to the FGF superfamily that is involved in cell proliferation and differentiation, neural development, angiogenesis, and metabolism. FGF21 requires β-Klotho as a co-receptor. Tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas express FGF21. Starvation increases hepatic expression of FGF21, which then acts centrally to increase hepatic gluconeogenesis. FGF21 also increases fatty acid oxidation. This may be relevant in cold exposure, when expression of FGF21 is induced...
April 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#6
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28330086/cloning-expression-purification-and-characterization-of-human-mitochondrial-carbonic-anhydrase-va
#7
Danish Idrees, Sudhir Kumar, Syed Abdul Arif Rehman, Samudrala Gourinath, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Carbonic anhydrase VA (CAVA) is a mitochondrial enzyme that catalyzes the reversible hydration of CO2 to produce HCO3(-) and proton. CAV is primarily involved in several biosynthetic processes such as ureagenesis, gluconeogenesis and lipogenesis by providing bicarbonate ion. Here, we report a new strategy for cloning, expression and purification for CAVA in the bacterial system followed by its biophysical characterization. The cDNA of CAVA, a 801 nucleotide long that encodes a 267-amino acid polypeptide of molecular mass of 30-kDa (excluding signal peptide), was sub-cloned in the expression vector pET21c and transformed into Escherichia coli strain BL21 (DE3) for expression...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329008/insulin-and-diet-induced-changes-in-the-ubiquitin-modified-proteome-of-rat-liver
#8
Shilpa R Nagarajan, Amanda E Brandon, Jessie A McKenna, Harrison C Shtein, Thinh Q Nguyen, Eurwin Suryana, Philip Poronnik, Gregory J Cooney, Darren N Saunders, Andrew J Hoy
Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28324010/separating-the-anti-inflammatory-and-diabetogenic-effects-of-glucocorticoids-through-lxr%C3%AE-antagonism
#9
Rucha Patel, Lilia Magomedova, Ricky Tsai, Stéphane Angers, Arturo Orellana, Carolyn L Cummins
Synthetic glucocorticoids (GCs) including dexamethasone (DEX) are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The glucocorticoid receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX, but still sensitive to its immunosuppressive actions...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323915/insulin-igf-1-and-gh-receptors-are-altered-in-an-adipose-tissue-depot-specific-manner-in-male-mice-with-modified-gh-action
#10
Rikke Hjortebjerg, Darlene E Berryman, Ross Comisford, Stuart J Frank, Edward O List, Mette Bjerre, Jan Frystyk, John J Kopchick
Growth hormone (GH) is an important determinant of glucose homeostasis and adipose tissue (AT) function. Using seven-month-old bovine GH transgenic (bGH) mice and GH receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression patterns of proteins involved in the interrelated signaling pathways of GH, insulin-like growth factor-1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice that may explain why GH effects depend on AT location...
February 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322845/metformin-like-antidiabetic-cardio-protective-and-non-glycemic-effects-of-naringenin-molecular-and-pharmacological-insights
#11
REVIEW
Annah Nsoaki Nyane, Thabiso Bethwel Tlaila, Tanki Gabriel Malefane, Dudu Edith Ndwandwe, Peter Mark Oroma Owira
Metformin is a widely used drug for the treatment of type 2 diabetes (T2D). Its blood glucose-lowering effects are initially due to inhibition of hepatic glucose production and increased peripheral glucose utilization. Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular complications in patients with diabetes. Adenosine Monophosphate Activated-Protein Kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism...
March 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322470/anti-inflammatory-and-antioxidant-actions-of-copaiba-oil-are-related-to-liver-cell-modifications-in-arthritic-rats
#12
Cristiane V de Castro Ghizoni, Ana P Arssufi Ames, Osmar A Lameira, Ciomar A Bersani Amado, Anacharis B de Sá Nakanishi, Lívia Bracht, Maria R Marçal Natali, Rosane M Peralta, Adelar Bracht, Jurandir F Comar
The present study investigated the action of copaiba oil (Copaifera reticulata) on the systemic inflammation, oxidative status and liver cell metabolism of rats with adjuvant-induced arthritis. The later is an experimental autoimmune pathology that shares many features with the human rheumatoid arthritis. Holtzman rats were distributed into the following groups: control (healthy) rats; control rats treated with copaiba oil at the doses of 0.58 and 1.15 g · Kg(-1) , arthritic rats, and arthritic rats treated with copaiba oil (0...
March 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28317891/hepatic-mitochondrial-dysfunction-is-a-feature-of-glycogen-storage-disease-type-ia-gsdia
#13
Benjamin L Farah, Rohit A Sinha, Yajun Wu, Brijesh K Singh, Andrea Lim, Masahiro Hirayama, Dustin J Landau, Boon Huat Bay, Dwight D Koeberl, Paul M Yen
Glycogen storage disease type Ia (GSDIa, von Gierke disease) is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, an enzyme which catalyses the final step of gluconeogenesis and glycogenolysis. Clinically, GSDIa is characterized by fasting hypoglycaemia and hepatic glycogen and triglyceride overaccumulation. The latter leads to steatohepatitis, cirrhosis, and the formation of hepatic adenomas and carcinomas. Currently, little is known about the function of various organelles and their impact on metabolism in GSDIa...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317366/-research-progress-on-forkhead-box-protein-o1-and-bone-metabolism
#14
Shu Linjing, Wu Yingying, Tan Zhen, Gong Ping
Recent studies found that forkhead box protein O1 (FoxO1) does not only demonstrate important biological functions in cell proliferation, gluconeogenesis, energy metabolism, and oxidative stress, but it also plays a vital role in the remodeling process of bones. FoxO1 can regulate bone mass by affecting osteoblasts, osteoclasts, and precursor cells. In this article, we review the role of FoxO1 in bone metabolism and elucidate its underlying mechanism.
August 1, 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28315483/functional-proteomic-analysis-of-corticosteroid-pharmacodynamics-in-rat-liver-relationship-to-hepatic-stress-signaling-energy-regulation-and-drug-metabolism
#15
Vivaswath S Ayyar, Richard R Almon, Debra C DuBois, Siddharth Sukumaran, Jun Qu, William J Jusko
Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL)...
March 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28314100/attenuated-mtor-signaling-and-enhanced-glucose-homeostasis-by-dietary-supplementation-with-lotus-seedpod-oligomeric-procyanidins-in-streptozotocin-stz-induced-diabetic-mice
#16
Xiaopeng Li, Yong Sui, Qian Wu, Bijun Xie, Zhida Sun
This study investigated the protective role of lotus seedpod oligomeric procyanidins (LSOPC) and synbiotics (Bifidobacterium Bb-12 and xylo-oligosaccharide) against high fat and streptozotocin (STZ)-induced diabetes. Administration of LSOPC or synbiotics have no effect on blood glucose in normal mice. Treatments with LSOPC for 12 weeks markedly reduced blood glucose, FFA, endotoxin, GHbA1c and improved glucose homeostasis, lipid metabolism and insulin level. In addition, administration of LSOPC significantly reversed the increase of mTOR and p66Shc in liver, skeletal muscle and white adipose tissue (WAT)...
March 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28306139/the-tir-bb-loop-mimetic-as-1-prevents-nonalcoholic-steatohepatitis-and-hepatic-insulin-resistance-by-inhibiting-nlrp3-asc-inflammasome-activation
#17
Xiaolu Wang, Yun Gao, Juan Song, Chao Tang, Man Wang, Linli Que, Li Liu, Guoqing Zhu, Qi Chen, Yong Yao, Yong Xu, Jiantao Li, Yuehua Li
BACKGROUND AND PURPOSE: Non-alcoholic steatohepatitis (NASH) is characterized by excessive intracellular lipid accumulation, inflammation and hepatic insulin resistance. Considering the rising prevalence of NASH worldwide, it is urgent to find novel interventional approaches. The pro-inflammatory cytokine IL-1β, generated and released from the Kupffer cells, is considered to be an initiating event in NASH. AS-1, a synthetic low-molecule mimetic to myeloid differentiation primary response gene 88 (MyD88), has been reported to disrupt the IL-1R-MyD88 interaction...
March 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28302863/transfer-of-dysbiotic-gut-microbiota-has-beneficial-effects-on-host-liver-metabolism
#18
Simon Nicolas, Vincent Blasco-Baque, Audren Fournel, Jerome Gilleron, Pascale Klopp, Aurelie Waget, Franck Ceppo, Alysson Marlin, Roshan Padmanabhan, Jason S Iacovoni, François Tercé, Patrice D Cani, Jean-François Tanti, Remy Burcelin, Claude Knauf, Mireille Cormont, Matteo Serino
Gut microbiota dysbiosis has been implicated in a variety of systemic disorders, notably metabolic diseases including obesity and impaired liver function, but the underlying mechanisms are uncertain. To investigate this question, we transferred caecal microbiota from either obese or lean mice to antibiotic-free, conventional wild-type mice. We found that transferring obese-mouse gut microbiota to mice on normal chow (NC) acutely reduces markers of hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non-inoculated mice, a phenotypic trait blunted in conventional NOD2 KO mice...
March 16, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28300770/transglycosylated-starch-improves-insulin-response-and-alters-lipid-and-amino-acid-metabolome-in-a-growing-pig-model
#19
Monica A Newman, Qendrim Zebeli, Eva Eberspächer, Dietmar Grüll, Timea Molnar, Barbara U Metzler-Zebeli
Due to the functional properties and physiological effects often associated with chemically modified starches, significant interest lies in their development for incorporation in processed foods. This study investigated the effect of transglycosylated cornstarch (TGS) on blood glucose, insulin, and serum metabolome in the pre- and postprandial phase in growing pigs. Eight jugular vein-catheterized barrows were fed two diets containing 72% purified starch (waxy cornstarch (CON) or TGS). A meal tolerance test (MTT) was performed with serial blood sampling for glucose, insulin, lipids, and metabolome profiling...
March 16, 2017: Nutrients
https://www.readbyqxmd.com/read/28297678/roles-for-cell-cell-adhesion-and-contact-in-obesity-induced-hepatic-myeloid-cell-accumulation-and-glucose-intolerance
#20
Yasutaka Miyachi, Kyoichiro Tsuchiya, Chikara Komiya, Kumiko Shiba, Noriko Shimazu, Shinobu Yamaguchi, Michiyo Deushi, Mizuko Osaka, Kouji Inoue, Yuta Sato, Sayaka Matsumoto, Junichi Kikuta, Kenjiro Wake, Masayuki Yoshida, Masaru Ishii, Yoshihiro Ogawa
Obesity promotes infiltration of inflammatory cells into various tissues, leading to parenchymal and stromal cell interaction and development of cellular and organ dysfunction. Liver sinusoidal endothelial cells (LSECs) are the first cells that contact portal blood cells and substances in the liver, but their functions in the development of obesity-associated glucose metabolism remain unclear. Here, we find that LSECs are involved in obesity-associated accumulation of myeloid cells via VLA-4-dependent cell-cell adhesion...
March 14, 2017: Cell Reports
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