Donald McClain

Summary

Affiliation: University of Utah
Country: USA

Publications

  1. pmc Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis
    Jingyu Huang
    Departments of Medicine and Biochemistry, University of Utah School of Medicine, Salt Lake City, USA
    Diabetes 60:80-7. 2011
  2. pmc Iron regulates glucose homeostasis in liver and muscle via AMP-activated protein kinase in mice
    Jingyu Huang
    Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
    FASEB J 27:2845-54. 2013
  3. pmc Manganese supplementation protects against diet-induced diabetes in wild type mice by enhancing insulin secretion
    Soh Hyun Lee
    Departments of Internal Medicine and Biochemistry, Veterans Affairs Medical Center, Salt Lake City, UT 84132, USA
    Endocrinology 154:1029-38. 2013
  4. ncbi request reprint Hexosamines stimulate leptin production in transgenic mice
    D A McClain
    Department of Medicine, University of Utah, Salt Lake City 84132, USA
    Endocrinology 141:1999-2002. 2000
  5. ncbi request reprint Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis
    Robert 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
  6. pmc Bridging the gap between basic and clinical investigation
    Donald 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
  7. ncbi request reprint Hexosamines as mediators of nutrient sensing and regulation in diabetes
    Donald 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
  8. ncbi request reprint Adipocytes with increased hexosamine flux exhibit insulin resistance, increased glucose uptake, and increased synthesis and storage of lipid
    Donald 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
  9. ncbi request reprint Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistance
    Mark Hazel
    Department of Medicine, University of Utah, Salt Lake City, Utah 84132, USA
    Endocrinology 145:2118-28. 2004
  10. pmc Iron-mediated inhibition of mitochondrial manganese uptake mediates mitochondrial dysfunction in a mouse model of hemochromatosis
    Hani A Jouihan
    Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
    Mol Med 14:98-108. 2008

Collaborators

Detail Information

Publications34

  1. pmc Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis
    Jingyu 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...
  2. pmc Iron regulates glucose homeostasis in liver and muscle via AMP-activated protein kinase in mice
    Jingyu 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...
  3. pmc Manganese supplementation protects against diet-induced diabetes in wild type mice by enhancing insulin secretion
    Soh Hyun Lee
    Departments of Internal Medicine and Biochemistry, Veterans Affairs Medical Center, Salt Lake City, UT 84132, USA
    Endocrinology 154:1029-38. 2013
    ....
  4. ncbi request reprint Hexosamines stimulate leptin production in transgenic mice
    D 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...
  5. ncbi request reprint Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis
    Robert 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...
  6. pmc Bridging the gap between basic and clinical investigation
    Donald 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...
  7. ncbi request reprint Hexosamines as mediators of nutrient sensing and regulation in diabetes
    Donald 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...
  8. ncbi request reprint Adipocytes with increased hexosamine flux exhibit insulin resistance, increased glucose uptake, and increased synthesis and storage of lipid
    Donald 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...
  9. ncbi request reprint Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistance
    Mark 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...
  10. pmc Iron-mediated inhibition of mitochondrial manganese uptake mediates mitochondrial dysfunction in a mouse model of hemochromatosis
    Hani 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...
  11. ncbi request reprint Increased glucose disposal and AMP-dependent kinase signaling in a mouse model of hemochromatosis
    Jingyu 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...
  12. pmc Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia
    Donald 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...
  13. ncbi request reprint Hexosamines regulate sensitivity of glucose-stimulated insulin secretion in beta-cells
    Robert 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...
  14. pmc PAS kinase is required for normal cellular energy balance
    Huai 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...
  15. ncbi request reprint Hyperglycemia and inhibition of glycogen synthase in streptozotocin-treated mice: role of O-linked N-acetylglucosamine
    Glendon 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...
  16. pmc Increased strength and physical performance with eccentric training in women with impaired glucose tolerance: a pilot study
    Robin 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)...
  17. ncbi request reprint Utility of ultrasound-guided fine-needle aspiration of parathyroid adenomas for localization before minimally invasive parathyroidectomy
    Devaprabu 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...
  18. pmc Contribution of insulin and Akt1 signaling to endothelial nitric oxide synthase in the regulation of endothelial function and blood pressure
    J 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
    ....
  19. pmc Dietary iron restriction or iron chelation protects from diabetes and loss of beta-cell function in the obese (ob/ob lep-/-) mouse
    Robert 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...
  20. ncbi request reprint Transgenic mice overexpressing the rate-limiting enzyme for hexosamine synthesis in skeletal muscle or adipose tissue exhibit total body insulin resistance
    Robert 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...
  21. ncbi request reprint Chronic hexosamine flux stimulates fatty acid oxidation by activating AMP-activated protein kinase in adipocytes
    Bai 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...
  22. pmc Systemic PPARĪ³ deletion impairs circadian rhythms of behavior and metabolism
    Guangrui 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 PPARĪ³ in the coordinated control of circadian clocks and metabolic pathways...
  23. ncbi request reprint Insulin resistance of glycogen synthase mediated by o-linked N-acetylglucosamine
    Glendon 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...
  24. pmc Regulation of Akt signaling by O-GlcNAc in euglycemia
    Yudi 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...
  25. pmc Protein modification by O-linked GlcNAc reduces angiogenesis by inhibiting Akt activity in endothelial cells
    Bai 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...
  26. ncbi request reprint A role for the transcriptional coactivator PGC-1alpha in muscle refueling
    Adam 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...
  27. pmc Overexpression of nuclear receptor SHP in adipose tissues affects diet-induced obesity and adaptive thermogenesis
    Imene 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...
  28. pmc The 3T3-L1 adipocyte glycogen proteome
    David 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...
  29. doi request reprint Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicity
    Arvind 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...
  30. ncbi request reprint Recipes for creating animal models of diabetic cardiovascular disease
    Willa 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
    ....
  31. pmc Up-regulation of O-GlcNAc transferase with glucose deprivation in HepG2 cells is mediated by decreased hexosamine pathway flux
    Rodrick 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...
  32. doi request reprint Glucose deprivation stimulates O-GlcNAc modification of proteins through up-regulation of O-linked N-acetylglucosaminyltransferase
    Rodrick 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...
  33. ncbi request reprint Cardiac expression of kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase inhibits glycolysis, promotes hypertrophy, impairs myocyte function, and reduces insulin sensitivity
    Rajakumar 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...
  34. pmc Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression
    Darrell 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...

Research Grants21

  1. IRON AND METABOLISM: ALTERED FUEL OXIDATION AND MITOCHONDRIAL DYSFUNCTION
    Donald A McClain; Fiscal Year: 2010
    ..Our data suggest that iron acts as a "poison" for mitochondria (the energy factories for cells) but also as a regulator of fat metabolism. ..
  2. IRON AND METABOLISM: ALTERED FUEL OXIDATION AND MITOCHONDRIAL DYSFUNCTION
    Donald McClain; Fiscal Year: 2009
    ..Our data suggest that iron acts as a "poison" for mitochondria (the energy factories for cells) but also as a regulator of fat metabolism. ..
  3. DIABETES IN HEMOCHROMATOSIS: PREVALENCE AND MECHANISMS
    Donald McClain; Fiscal Year: 2007
    ..These results will guide future studies to determine the role of these phenomena in type 2 diabetes. ..
  4. HEXOSAMINES, GLUCOSE TOXICITY AND INSULIN RESISTANCE
    Donald McClain; Fiscal Year: 2009
    ..An extension of our earlier studies that showed sufficiency of the HBP in inducing insulin resistance, this transgenic model will determine the necessity of the pathway. ..
  5. HEXOSAMINES, GLUCOSE TOXICITY AND INSULIN RESISTANCE
    Donald A McClain; Fiscal Year: 2010
    ..The specific process that we are investigating is how the pathway regulated the storage of glucose as glycogen, an important aspect of regulating blood glucose levels ..
  6. DIABETES IN HEMOCHROMATOSIS: PREVALENCE AND MECHANISMS
    Donald 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. ..
  7. HEXOSAMINES, GLUCOSE TOXICITY AND INSULIN RESISTANCE
    Donald McClain; Fiscal Year: 2003
    ..4. The investigators will test the hypothesis that hexosamines exert their effects through O-linked glycosylation. ..
  8. HEXOSAMINES, GLUCOSE TOXICITY AND INSULIN RESISTANCE
    Donald A McClain; Fiscal Year: 2010
    ..An extension of our earlier studies that showed sufficiency of the HBP in inducing insulin resistance, this transgenic model will determine the necessity of the pathway. ..