Donald A. McClain, M.D., Ph.D.

Languages

  • English
  • German

Academic Information

  • Departments: Biochemistry - Adjunct Professor, Internal Medicine - Adjunct Professor
  • Divisions: Endocrinology and Metabolism

Board Certification

  • American Board of Internal Medicine (Sub: Endocrinology, Diabetes & Metabolism)
  • American Board of Internal Medicine (Internal Medicine)

Academic Office Information

  • (801) 581-6736
  • Radiobiology Administration
    Endocrinology
    40 N 2030 E, Room: 110
    Salt Lake City, UT 84112

Academic Bio

I received MD and PhD degrees from the Rockefeller University/ Cornell Medical School Biomedical Sciences Program in 1979, with thesis work performed in the laboratory of Nobel laureate Gerald Edelman. Training in Internal Medicine and Endocrinology were completed at Stanford and the University of California at San Diego. I came to the University of Utah after holding faculty positions at the Universities of California San Diego, Alabama at Birmingham and Mississippi. I am currently Professor of Medicine and Biochemistry at the University of Utah School of Medicine, where I hold the Bettilyon Chair in Diabetes Research. After serving as the Director of the Division of Endocrinology and Metabolism for eight years, in 2008 I assumed the positions of Associate Vice President for Clinical Research and the Directorship of the NIH-funded (CTSA) Center for Clinical and Translational Science. I participate in the national consortium as a co-chair for the Clinical Service Center Key Function Committee, co-chair of Strategic Goal Committee 5, and member of the CTSA Consortium Executive Committee. I have also served as Associate Editor of the journal Endocrinology and Chair of grant review panels of the NIH, VA, and American Diabetes Association.

My current research program, funded by the NIH and VA, is aimed at further understanding the pathogenesis of diabetes, obesity, and its complications, using both human studies and animal or cell culture models. Our current work in this area includes three projects: (1) How glucose regulates transcription and protein function through the hexosamine pathway of glucose metabolism; (2) How excess iron, a risk factor for diabetes, regulated metabolism, and; (3) How hypoxia regulates metabolism.

We have previously shown that artificially increasing hexosamine flux in the tissues responsible for fuel homeostasis recapitulates many of the central phenotypic characteristics of type 2 diabetes. We have shown that the basis for these effects is the modification of cytosolic and nuclear proteins by O-linked GlcNAc. We are currently engaged in work to more fully characterize the biochemical basis for these changes, concentrating on the transcriptional regulation, activation and subcellular partitioning of key enzymes of fuel homeostasis such as glycogen synthase and AMP-dependent kinase.

Our laboratory also studies the mechanisms by which high levels of iron, such as are seen in some hereditary conditions (e.g. hemochromatosis) and also with simple dietary iron overload, are associated with diabetes. To this end, we have discovered novel mechanisms by which iron regulates fat metabolism and impairs mitochondrial function. Current projects focus on the regulation by iron of adipokines, the circadian rhythm, and cellular signaling pathways involved in metabolic regulation.

Finally, because iron can exert some of its effects through the hypoxia signaling pathway, we are also studying the effects of hypoxia on metabolism in animal models and human populations that are adapted to high altitude.

Education History

Type School Degree
Fellowship University of California - San Diego
Endo/Metabolism
Fellow
Residency Stanford University Medical Center
Internal Medicine
Resident
Internship Stanford University Medical Center
Intern
Doctoral Training Cornell University College of Arts and Sciences
Cell Biology
Ph.D.
Professional Medical Cornell University Medical College
Medicine
M.D.
Undergraduate Haverford College
B.A.

Selected Publications

Journal Article

  1. Regional muscle glucose uptake remains elevated one week after cessation of resistance training independent of altered insulin sensitivity response in older adults with type 2 diabetes.Marcus RL, Addison O, LaStayo PC, Hungerford R, Wende AR, Hoffman JM, Abel ED, McClain DA (2013). Regional muscle glucose uptake remains elevated one week after cessation of resistance training independent of altered insulin sensitivity response in older adults with type 2 diabetes. J Endocrinol Invest, 36(2), 111-7.
  2. Metabolic insight into mechanisms of high-altitude adaptation in Tibetans.Ge RL, Simonson TS, Cooksey RC, Tanna U, Qin G, Huff CD, Witherspoon DJ, Xing J, Zhengzhong B, Prchal JT, Jorde LB, McClain DA (2012). Metabolic insight into mechanisms of high-altitude adaptation in Tibetans. Mol Genet Metab, 106(2), 244-7.
  3. Early mitochondrial adaptations in skeletal muscle to diet-induced obesity are strain dependent and determine oxidative stress and energy expenditure but not insulin sensitivity.Boudina S, Sena S, Sloan C, Tebbi A, Han YH, ONeill BT, Cooksey RC, Jones D, Holland WL, McClain DA, Abel ED (2012). Early mitochondrial adaptations in skeletal muscle to diet-induced obesity are strain dependent and determine oxidative stress and energy expenditure but not insulin sensitivity. Endocrinology, 153(6), 2677-88.
  4. Increased hexosamine pathway flux and high fat feeding are not additive in inducing insulin resistance: evidence for a shared pathway.Cooksey RC, McClain DA (2011). Increased hexosamine pathway flux and high fat feeding are not additive in inducing insulin resistance: evidence for a shared pathway. Amino Acids, 40(3), 841-6.
  5. 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.Huang J, Jones D, Luo B, Sanderson M, Soto J, Abel ED, Cooksey RC, McClain DA (2011). 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. Diabetes, 60(1), 80-7.
  6. Muscle damage and muscle remodeling: no pain, no gain?Flann KL, LaStayo PC, McClain DA, Hazel M, Lindstedt SL (2011). Muscle damage and muscle remodeling: no pain, no gain? J Exp Biol, 214(Pt 4), 674-9.
  7. Pleiotropic and Age-dependent Effects of Decreased Protein Modification by O-Linked N-Acetylglucosamine on Pancreatic {beta}-Cell Function and Vascularization.Soesanto Y, Luo B, Parker G, Jones D, Cooksey RC, McClain DA (2011). Pleiotropic and Age-dependent Effects of Decreased Protein Modification by O-Linked N-Acetylglucosamine on Pancreatic {beta}-Cell Function and Vascularization. J Biol Chem, 286(29), 26118-26.
  8. McClain DA, Taylor RP, Soesanto Y, Luo B (2010). Metabolic Regulation by the Hexosamine Biosynthesis/O-Linked N-Acetyl Glucosamine Pathway. Curr Signal Transduct Ther, 5(1), 3-11.
  9. Bridging the gap between basic and clinical investigation.McClain DA (2010). Bridging the gap between basic and clinical investigation. Trends Biochem Sci, 35(4), 187-8.
  10. Dietary iron restriction or iron chelation protects from diabetes and loss of beta-cell function in the obese (ob/ob lep-/-) mouse.Cooksey RC, Jones D, Gabrielsen S, Huang J, Simcox JA, Luo B, Soesanto Y, Rienhoff H, Abel ED, McClain DA (2010). Dietary iron restriction or iron chelation protects from diabetes and loss of beta-cell function in the obese (ob/ob lep-/-) mouse. Am J Physiol Endocrinol Metab, 298(6), E1236-43.
  11. Taylor RP, Geisler TS, Chambers JH, McClain DA (2009). Up-regulation of O-GlcNAc Transferase with Glucose Deprivation in HepG2 Cells Is Mediated by Decreased Hexosamine Pathway Flux. PMID: 19073609. Biol Chem, 284(6), 3425-32.

Review

  1. Genetic determinants of Tibetan high-altitude adaptation.Simonson TS, McClain DA, Jorde LB, Prchal JT (2012). Genetic determinants of Tibetan high-altitude adaptation. [Review]. Hum Genet, 131(4), 527-33.