Genomes and Genes
Affiliation: University of Utah
- Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosisJingyu Huang
Departments of Medicine and Biochemistry, University of Utah School of Medicine, Salt Lake City, USA
Diabetes 60:80-7. 2011..This effect by itself is not sufficient, however, to fully explain the diabetes risk phenotype associated with all forms of iron overload...
- Iron regulates glucose homeostasis in liver and muscle via AMP-activated protein kinase in miceJingyu Huang
Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
FASEB J 27:2845-54. 2013..In summary, a diet high in iron improves glucose tolerance by activating AMPK through mechanisms that include deacetylation...
- Manganese supplementation protects against diet-induced diabetes in wild type mice by enhancing insulin secretionSoh Hyun Lee
Departments of Internal Medicine and Biochemistry, Veterans Affairs Medical Center, Salt Lake City, UT 84132, USA
Endocrinology 154:1029-38. 2013....
- Hexosamines stimulate leptin production in transgenic miceD A McClain
Department of Medicine, University of Utah, Salt Lake City 84132, USA
Endocrinology 141:1999-2002. 2000..2 in control, arbitrary units normalized to actin, p < 0.007). Despite increased leptin, the transgenic animals did not have lower body fat content. We conclude that hexosamine flux in fat regulates leptin synthesis and secretion...
- Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosisRobert C Cooksey
Division of Endocrinology, University of Utah School of Medicine, 30 North 2030 East, Salt Lake City, Utah 84132
Endocrinology 145:5305-12. 2004..This abnormality alone, however, is insufficient to cause diabetes...
- Bridging the gap between basic and clinical investigationDonald A McClain
Center for Clinical and Translational Science, 30 North 2030 East, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
Trends Biochem Sci 35:187-8. 2010..This article focuses on the increasing importance of effective communication between scientists and their clinical colleagues. Some recent and innovative programs to facilitate these interactions are also discussed...
- Hexosamines as mediators of nutrient sensing and regulation in diabetesDonald A McClain
Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Utah and VA Medical Center, 50 N Medical Drive, 4C116, Salt Lake City, UT 84132, USA
J Diabetes Complications 16:72-80. 2002..These results suggest a mechanism by which chronic overnutrition leads to the phenotype of Type 2 diabetes...
- Adipocytes with increased hexosamine flux exhibit insulin resistance, increased glucose uptake, and increased synthesis and storage of lipidDonald A McClain
Veterans Affairs Medical Center, Department of Medicine, 30 N 2030 East, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
Am J Physiol Endocrinol Metab 288:E973-9. 2005..05). We conclude that the hexosamine signaling pathway upregulates fat storage in adipocytes in states of carbohydrate excess, in part by increasing GLUT4 and glucose uptake and by augmenting fatty acid synthesis...
- Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistanceMark Hazel
Department of Medicine, University of Utah, Salt Lake City, Utah 84132, USA
Endocrinology 145:2118-28. 2004..Changes in serum adiponectin correlate with the insulin resistance of the transgenic animals...
- Iron-mediated inhibition of mitochondrial manganese uptake mediates mitochondrial dysfunction in a mouse model of hemochromatosisHani A Jouihan
Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
Mol Med 14:98-108. 2008..These data suggest a novel mechanism of iron-induced cellular dysfunction, namely altered mitochondrial uptake of other metal ions...
- Increased glucose disposal and AMP-dependent kinase signaling in a mouse model of hemochromatosisJingyu Huang
Department of Biochemistry, The University of Utah School of Medicine, Salt Lake City, UT 84132, USA
J Biol Chem 282:37501-7. 2007..Instead, the Hfe(-/-) mice demonstrate increased adiponectin levels and activation of AMP-dependent kinase...
- Altered glycan-dependent signaling induces insulin resistance and hyperleptinemiaDonald A McClain
Department of Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT 84112, USA
Proc Natl Acad Sci U S A 99:10695-9. 2002..These data support the proposal that O-linked GlcNAc transferase participates in a hexosamine-dependent signaling pathway that is linked to insulin resistance and leptin production...
- Hexosamines regulate sensitivity of glucose-stimulated insulin secretion in beta-cellsRobert C Cooksey
Veterans Administration Medical Center and Division of Endocrinology and Metabolism, University of Utah School of Medicine, 30 N 2030 East, Salt Lake City, UT 84132, USA
Am J Physiol Endocrinol Metab 290:E334-40. 2006..Prolonged excess hexosamine flux results in glucose desensitization and mimics glucose toxicity...
- PAS kinase is required for normal cellular energy balanceHuai Xiang Hao
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Proc Natl Acad Sci U S A 104:15466-71. 2007..We therefore hypothesize that PASK acts in a cell-autonomous manner to maintain cellular energy homeostasis and is a potential therapeutic target for metabolic disease...
- Increased strength and physical performance with eccentric training in women with impaired glucose tolerance: a pilot studyRobin L Marcus
Department of Physical Therapy, University of Utah, Salt Lake City, Utah, Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah
J Womens Health (Larchmt) 18:253-60. 2009..This study assessed the effect of repeated ECC on IS, muscle mass, and function in postmenopausal women with impaired glucose tolerance (IGT)...
- Contribution of insulin and Akt1 signaling to endothelial nitric oxide synthase in the regulation of endothelial function and blood pressureJ David Symons
College of Health, University of Utah School of Medicine, 30 N 2030 E, Salt Lake City, UT 84132, USA
Circ Res 104:1085-94. 2009....
- Utility of ultrasound-guided fine-needle aspiration of parathyroid adenomas for localization before minimally invasive parathyroidectomyDevaprabu Abraham
Division of Endocrinology, Department of Medicine, Veterans Affairs Medical Center and University of Utah, Salt Lake City, UT, USA
Endocr Pract 13:333-7. 2007..To determine the sensitivity and specificity of ultrasound (US)-guided fine-needle aspiration (FNA) and measurement of parathyroid hormone (PTH) in the aspirate (FNA/PTH) as a preoperative localization procedure...
- Hyperglycemia and inhibition of glycogen synthase in streptozotocin-treated mice: role of O-linked N-acetylglucosamineGlendon Parker
Veterans Affairs Medical Center and Division of Endocrinology, University of Utah School of Medicine, 30 North, 2030 East, Salt Lake City, UT 84132, USA
J Biol Chem 279:20636-42. 2004..05). The findings demonstrate that O-GlcNAc has a role in the regulation of glycogen synthase both in normoglycemia and diabetes...
- Transgenic mice overexpressing the rate-limiting enzyme for hexosamine synthesis in skeletal muscle or adipose tissue exhibit total body insulin resistanceRobert C Cooksey
VA Medical Center and Department of Medicine, University of Utah, Salt Lake City 84132, USA
Ann N Y Acad Sci 967:102-11. 2002..The results suggest a mechanism by which chronic overnutrition leads to the phenotype of type 2 diabetes...
- Chronic hexosamine flux stimulates fatty acid oxidation by activating AMP-activated protein kinase in adipocytesBai Luo
Division of Endocrinology, University of Utah School of Medicine and Veterans Affairs Medical Center, Salt Lake City, Utah 84132, USA
J Biol Chem 282:7172-80. 2007..Moreover, removal of O-GlcNAc by hexosaminidase reduced AMPK activity. We conclude that chronically high hexosamine flux stimulates fatty acid oxidation by activating AMPK in adipocytes, in part through O-linked glycosylation...
- Dietary iron restriction or iron chelation protects from diabetes and loss of beta-cell function in the obese (ob/ob lep-/-) mouseRobert C Cooksey
Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
Am J Physiol Endocrinol Metab 298:E1236-43. 2010..We conclude that, even at "normal" levels, iron exerts detrimental effects on beta-cell function that are reversible with dietary restriction or pharmacotherapy...
- Insulin resistance of glycogen synthase mediated by o-linked N-acetylglucosamineGlendon J Parker
Veterans Affairs Medical Center and Division of Endocrinology, University of Utah School of Medicine, Salt Lake City 84132, USA
J Biol Chem 278:10022-7. 2003..We conclude that O-GlcNAc modification of glycogen synthase results in the retention of the enzyme in a glucose 6-phosphate-dependent state and contributes to the reduced activation of the enzyme in insulin resistance...
- Regulation of Akt signaling by O-GlcNAc in euglycemiaYudi A Soesanto
Division of Endocrinology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
Am J Physiol Endocrinol Metab 295:E974-80. 2008..Together, these data suggest that O-GlcNAc regulates Akt signaling in hepatic models under euglycemic conditions...
- Protein modification by O-linked GlcNAc reduces angiogenesis by inhibiting Akt activity in endothelial cellsBai Luo
Division of Endocrinology, University of Utah, Salt Lake City, UT 84132, USA
Arterioscler Thromb Vasc Biol 28:651-7. 2008..Impaired angiogenesis is well-recognized in diabetes; however, the mechanisms are not completely defined. Here, we investigated the role of protein O-GlcNAc modification in angiogenesis...
- A role for the transcriptional coactivator PGC-1alpha in muscle refuelingAdam R Wende
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 282:36642-51. 2007..These findings identify PGC-1alpha as a critical regulator of skeletal muscle fuel stores...
- Overexpression of nuclear receptor SHP in adipose tissues affects diet-induced obesity and adaptive thermogenesisImene Tabbi-Anneni
Department of Medicine, and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
Am J Physiol Endocrinol Metab 298:E961-70. 2010..In conclusion, SHP activation in adipocytes strongly affects weight gain and diet-induced obesity. Developing a synthetic compound to antagonize the effect of SHP may prove to be useful in treating obesity...
- Systemic PPARγ deletion impairs circadian rhythms of behavior and metabolismGuangrui Yang
Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America
PLoS ONE 7:e38117. 2012..Together, these results support an essential role of PPARγ in the coordinated control of circadian clocks and metabolic pathways...
- The 3T3-L1 adipocyte glycogen proteomeDavid Stapleton
University of Utah School of Medicine, Rm 4C464B SOM, 30 N 1900 E, Salt Lake City, Utah 84132, USA
Proteome Sci 11:11. 2013..To provide new molecular insights into the role of adipocyte glycogen we analyzed the glycogen-associated proteome from differentiated 3T3-L1-adipocytes...
- Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicityArvind Shakya
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
Nat Cell Biol 11:320-7. 2009..We show that these metabolic changes directly oppose tumorigenicity. Collectively, our findings show that Oct1, the genes it regulates and the pathways these genes affect could be used as targets for new modes of cancer therapy...
- Recipes for creating animal models of diabetic cardiovascular diseaseWilla Hsueh
Division of Endocrinology, Diabetes, and Hypertension, The David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Circ Res 100:1415-27. 2007....
- Up-regulation of O-GlcNAc transferase with glucose deprivation in HepG2 cells is mediated by decreased hexosamine pathway fluxRodrick P Taylor
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
J Biol Chem 284:3425-32. 2009..We conclude that deglycosylation of proteins within the first few hours of glucose deprivation promotes ncOGT induction. These findings suggest a novel negative feedback regulatory loop for OGT and O-GlcNAc regulation...
- Glucose deprivation stimulates O-GlcNAc modification of proteins through up-regulation of O-linked N-acetylglucosaminyltransferaseRodrick P Taylor
Departments of Biochemistry and Medicine, University of Utah School of Medicine, 30 N 2030 East, Salt Lake City, UT 84132, USA
J Biol Chem 283:6050-7. 2008..03). We conclude that increased O-GlcNAc modification stimulated by glucose deprivation results from increased OGT and decreased O-GlcNAcase levels and that these changes affect cell metabolism, thus inactivating glycogen synthase...
- Cardiac expression of kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase inhibits glycolysis, promotes hypertrophy, impairs myocyte function, and reduces insulin sensitivityRajakumar V Donthi
Department of Pediatrics Diabetes Research, University of Louisville, School of Medicine, Louisville, Kentucky 40202, USA
J Biol Chem 279:48085-90. 2004..In addition, metabolic and signaling responses to insulin were significantly decreased...
- Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expressionDarrell D Belke
Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada
J Clin Invest 109:629-39. 2002..Insulin may also modulate cardiac myocyte metabolism through paracrine mechanisms by activating insulin receptors in other cell types within the heart...
- DIABETES IN HEMOCHROMATOSIS: PREVALENCE AND MECHANISMSDonald McClain; Fiscal Year: 2006..Insulin resistance and HGP will be quantified by the hyperinsulinemic euglycemic clamp and stable isotope techniques in subjects with hemochromatosis who have normal or IGT, with or without hepatic involvement. ..
- DIABETES IN HEMOCHROMATOSIS: PREVALENCE AND MECHANISMSDonald McClain; Fiscal Year: 2007..These results will guide future studies to determine the role of these phenomena in type 2 diabetes. ..