JERROLD MICHAEL OLEFSKY

Summary

Affiliation: University of California
Country: USA

Publications

  1. doi request reprint Fat talks, liver and muscle listen
    Jerrold M Olefsky
    University of California San Diego, La Jolla, CA 92093 0673, USA
    Cell 134:914-6. 2008
  2. ncbi request reprint Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects
    Gautam K Bandyopadhyay
    Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Diego, 9500 Gilman Dr, La Jolla, 92093, USA
    Diabetes 55:2277-85. 2006
  3. pmc Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats
    Jian Jiao
    NGM Biopharmaceuticals, Inc, South San Francisco, California, USA
    Diabetes 62:1074-83. 2013
  4. ncbi request reprint Prospects for research in diabetes mellitus
    J M Olefsky
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA
    JAMA 285:628-32. 2001
  5. ncbi request reprint Cell signaling. A new way to burn fat
    Jaap G Neels
    Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0673, USA
    Science 312:1756-8. 2006
  6. pmc Novel liver-specific TORC2 siRNA corrects hyperglycemia in rodent models of type 2 diabetes
    Maziyar Saberi
    Univ of California San Diego, Dept of Medicine, 9500 Gilman Dr, SCR225, La Jolla CA 92093, USA
    Am J Physiol Endocrinol Metab 297:E1137-46. 2009
  7. doi request reprint IKKepsilon: a bridge between obesity and inflammation
    Jerrold M Olefsky
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 138:834-6. 2009
  8. doi request reprint Macrophages, inflammation, and insulin resistance
    Jerrold M Olefsky
    Department of Medicine, University of California San Diego, La Jolla, CA 92093 0651, USA
    Annu Rev Physiol 72:219-46. 2010
  9. pmc Increased macrophage migration into adipose tissue in obese mice
    Da Young Oh
    Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Diabetes 61:346-54. 2012
  10. pmc The US's changing competitiveness in the biomedical sciences
    Jerrold M Olefsky
    University of California at San Diego, Department of Medicine, La Jolla, CA 92093 0673, USA
    J Clin Invest 117:270-6. 2007

Research Grants

  1. TRAINING PROGRAM IN DIABETES RESEARCH
    Jerrold Olefsky; Fiscal Year: 2007
  2. INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM
    Jerrold Olefsky; Fiscal Year: 2007
  3. Estrogens and Insulin Resistance in Women
    Jerrold Olefsky; Fiscal Year: 2006
  4. Estrogen Effects in Insulin Target and Granulosa Cells
    Jerrold Olefsky; Fiscal Year: 2004
  5. INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM
    JERROLD MICHAEL OLEFSKY; Fiscal Year: 2010

Detail Information

Publications85

  1. doi request reprint Fat talks, liver and muscle listen
    Jerrold M Olefsky
    University of California San Diego, La Jolla, CA 92093 0673, USA
    Cell 134:914-6. 2008
    ..Cao et al. (2008) now take this concept a step further by identifying a fatty acid metabolite generated in adipose tissue that regulates insulin sensitivity in liver and muscle...
  2. ncbi request reprint Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects
    Gautam K Bandyopadhyay
    Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Diego, 9500 Gilman Dr, La Jolla, 92093, USA
    Diabetes 55:2277-85. 2006
    ....
  3. pmc Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats
    Jian Jiao
    NGM Biopharmaceuticals, Inc, South San Francisco, California, USA
    Diabetes 62:1074-83. 2013
    ..The present data highlight and support the significance of vagal inputs and intestinal hormone peptides toward normalization of glucose and lipid homeostasis after duodenal bypass surgery...
  4. ncbi request reprint Prospects for research in diabetes mellitus
    J M Olefsky
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA
    JAMA 285:628-32. 2001
    ..Also, the link between obesity and type 2 diabetes mandates a redoubled effort to understand the genetic and behavioral contributions to obesity...
  5. ncbi request reprint Cell signaling. A new way to burn fat
    Jaap G Neels
    Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0673, USA
    Science 312:1756-8. 2006
  6. pmc Novel liver-specific TORC2 siRNA corrects hyperglycemia in rodent models of type 2 diabetes
    Maziyar Saberi
    Univ of California San Diego, Dept of Medicine, 9500 Gilman Dr, SCR225, La Jolla CA 92093, USA
    Am J Physiol Endocrinol Metab 297:E1137-46. 2009
    ..In conclusion, these results demonstrate the importance of TORC2 in modulating HGP in vivo and highlight a novel, liver-specific siRNA approach for the potential treatment of hyperglycemia and type 2 diabetes...
  7. doi request reprint IKKepsilon: a bridge between obesity and inflammation
    Jerrold M Olefsky
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 138:834-6. 2009
    ..Chiang et al. (2009) now show that the IkappaB kinase IKKepsilon is an important link between obesity and inflammation and may be a new therapeutic target for treating obesity-related metabolic diseases...
  8. doi request reprint Macrophages, inflammation, and insulin resistance
    Jerrold M Olefsky
    Department of Medicine, University of California San Diego, La Jolla, CA 92093 0651, USA
    Annu Rev Physiol 72:219-46. 2010
    ..Strategies focused on inhibiting the inflammation/insulin resistance axis that otherwise preserve essential innate immune functions may hold promise for therapeutic intervention...
  9. pmc Increased macrophage migration into adipose tissue in obese mice
    Da Young Oh
    Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Diabetes 61:346-54. 2012
    ..Monocytes from obese mice are not programmed to become inflammatory ATMs but rather the increased proinflammatory ATM accumulation in obesity is in response to tissue signals...
  10. pmc The US's changing competitiveness in the biomedical sciences
    Jerrold M Olefsky
    University of California at San Diego, Department of Medicine, La Jolla, CA 92093 0673, USA
    J Clin Invest 117:270-6. 2007
  11. ncbi request reprint Decreased susceptibility to fatty acid-induced peripheral tissue insulin resistance in women
    J P Frias
    Department of Endocrinology and Metabolism, University of California-San Diego, Veterans Affairs Medical Center, 3350 La Jolla Village Dr, La Jolla, CA 92093, USA
    Diabetes 50:1344-50. 2001
    ..In summary, our findings suggest that although the effects on EGP appear comparable, the inhibitory effects of NEFA on peripheral tissue insulin sensitivity are observed in men but cannot be demonstrated in women...
  12. pmc Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency
    P D Miles
    Department of Surgery, University of California San Diego, San Diego, California 92103, USA
    J Clin Invest 105:287-92. 2000
    ....
  13. ncbi request reprint Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity
    T P Ciaraldi
    Department of Medicine, University of California San Diego, La Jolla 92093, USA
    J Clin Endocrinol Metab 82:1421-5. 1997
    ..In addition, this insulin resistance involves an impairment of the system by which adenosine acts to modulate insulin signal transduction...
  14. ncbi request reprint TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone
    P D Miles
    Department of Surgery, University of California, San Diego 92103, USA
    Diabetes 46:1678-83. 1997
    ..If TNF-alpha plays a role in the development of the obesity/NIDDM syndrome, troglitazone may prove useful in its treatment...
  15. ncbi request reprint Troglitazone prevents hyperglycemia-induced but not glucosamine-induced insulin resistance
    P D Miles
    Department of Surgery, University of California, San Diego, USA
    Diabetes 47:395-400. 1998
    ....
  16. ncbi request reprint Exercise-stimulated glucose turnover in the rat is impaired by glucosamine infusion
    P D Miles
    Department of Surgery, University of California San Diego, USA
    Diabetes 50:139-42. 2001
    ..In conclusion, the infusion of glucosamine, which is known to cause insulin resistance, also impaired exercise-induced glucose uptake. This inhibition was independent of hyperglycemia and FFA levels...
  17. ncbi request reprint Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles
    J Kusari
    Department of Medicine, University of California, La Jolla 92093
    J Biol Chem 266:5260-7. 1991
    ....
  18. pmc Synthesis of an organoinsulin molecule that can be activated by antibody catalysis
    D S Worrall
    Department of Medicine (0673, Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 98:13514-8. 2001
    ..We propose that these results are the foundation for an in vivo regulated system of insulin activation using the prohormone insulin(D) and catalytic antibody 38C2 with potential therapeutic application...
  19. ncbi request reprint Variance-modeled posterior inference of microarray data: detecting gene-expression changes in 3T3-L1 adipocytes
    A Hsiao
    Department of Bioengineering, UC San Diego, La Jolla, CA 92093, USA
    Bioinformatics 20:3108-27. 2004
    ....
  20. ncbi request reprint A functional assessment of insulin/insulin-like growth factor-I hybrid receptors
    B L Seely
    Department of Medicine, University of California San Diego, La Jolla 92093
    Endocrinology 136:1635-41. 1995
    ..In conclusion, IGF-I-stimulated insulin/IGF-I hybrid receptors function like IGF-I receptors, rather than like insulin receptors...
  21. pmc Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus
    J Kusari
    Department of Medicine, University of California, San Diego, La Jolla 92093
    J Clin Invest 88:1323-30. 1991
    ..Possibly, a subpopulation of NIDDM patients exists displaying variation in the GLUT-4 gene...
  22. ncbi request reprint Insulin and insulin-like growth factor I receptors utilize different G protein signaling components
    S Dalle
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093-0673, USA
    J Biol Chem 276:15688-95. 2001
    ..These results suggest that insulin receptors and IGF-IRs can function as G protein-coupled receptors and engage different G protein partners for downstream signaling...
  23. pmc Chronic endothelin-1 treatment leads to heterologous desensitization of insulin signaling in 3T3-L1 adipocytes
    K I Ishibashi
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093-0673, USA
    J Clin Invest 107:1193-202. 2001
    ....
  24. ncbi request reprint Insulin stimulates the tyrosine dephosphorylation of pp125 focal adhesion kinase
    T S Pillay
    Department of Medicine, University of California San Diego, La Jolla 92093 0673
    J Biol Chem 270:991-4. 1995
    ....
  25. ncbi request reprint beta -Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport
    T Imamura
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    J Biol Chem 276:43663-7. 2001
    ....
  26. pmc Insulin can regulate GLUT4 internalization by signaling to Rab5 and the motor protein dynein
    J Huang
    Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla, CA 92093-0673, USA
    Proc Natl Acad Sci U S A 98:13084-9. 2001
    ....
  27. ncbi request reprint Protein tyrosine phosphatase 1B interacts with the activated insulin receptor
    B L Seely
    Department of Medicine, University of California, San Diego, La Jolla, USA
    Diabetes 45:1379-85. 1996
    ..We conclude that PTP1B can associate directly with the activated insulin receptor at multiple different phosphotyrosine sites and that dephosphorylation by PTP1B may play a significant role in insulin receptor signal transduction...
  28. ncbi request reprint Insulin disrupts beta-adrenergic signalling to protein kinase A in adipocytes
    Jin Zhang
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
    Nature 437:569-73. 2005
    ..Chronically high insulin levels may disrupt the close apposition of beta-adrenergic receptors and PKA, identifying a new mechanism for crosstalk between heterologous signal transduction pathways...
  29. ncbi request reprint Topiramate treatment causes skeletal muscle insulin sensitization and increased Acrp30 secretion in high-fat-fed male Wistar rats
    Jason J Wilkes
    Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, 0673 UCSD, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Am J Physiol Endocrinol Metab 289:E1015-22. 2005
    ....
  30. ncbi request reprint Lentiviral short hairpin ribonucleic acid-mediated knockdown of GLUT4 in 3T3-L1 adipocytes
    Wei Liao
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, 92093, USA
    Endocrinology 147:2245-52. 2006
    ..These studies indicate that lentiviral shRNA constructs provide an excellent approach to deliver functional siRNAs into 3T3-L1 adipocytes for studying insulin signaling and adipocyte biology...
  31. pmc PPARdelta regulates glucose metabolism and insulin sensitivity
    Chih Hao Lee
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:3444-9. 2006
    ..The combined hepatic and peripheral actions of PPARdelta suggest new therapeutic approaches to treat type II diabetes...
  32. pmc Suppression of Egr-1 transcription through targeting of the serum response factor by oncogenic H-Ras
    Soon Young Shin
    Division of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan, Korea
    EMBO J 25:1093-103. 2006
    ..Our findings suggest a novel signaling mechanism by which prolonged activation of oncogenic H-Ras can trigger the loss of tumor suppressor Egr-1 through the PI3K pathway in NIH3T3 fibroblast model cell lines...
  33. ncbi request reprint Stressed out about obesity and insulin resistance
    Carl De Luca
    Nat Med 12:41-2; discussion 42. 2006
  34. pmc Inflamed fat: what starts the fire?
    Jaap G Neels
    Department of Medicine, Division of Endocrinology and Metabolism, UCSD, La Jolla, California 92093 0673, USA
    J Clin Invest 116:33-5. 2006
    ..In this issue of the JCI, Weisberg et al. show the importance of C-C motif chemokine receptor 2 (CCR2) in macrophage recruitment to adipose tissue and the development of obesity and its complications...
  35. ncbi request reprint JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes
    M T Audrey Nguyen
    Division of Endocrinology Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    J Biol Chem 280:35361-71. 2005
    ....
  36. ncbi request reprint Disruption of microtubules ablates the specificity of insulin signaling to GLUT4 translocation in 3T3-L1 adipocytes
    Jie Huang
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    J Biol Chem 280:42300-6. 2005
    ....
  37. ncbi request reprint Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance
    Lisa A Lesniewski
    Department of Endocrinology and Metabolism, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nat Med 13:455-62. 2007
    ..These studies show that macrophages are an important cell type in the induction of insulin resistance and that Cap has a modulatory role in this function...
  38. pmc Insulin sensitivity: modulation by nutrients and inflammation
    Simon Schenk
    Department of Medicine, Division of Endocrinology and Metabolism, UCSD, La Jolla, California 92093, USA
    J Clin Invest 118:2992-3002. 2008
    ..Overall, we provide our integrative perspective regarding how nutrients and obesity interact to regulate insulin sensitivity...
  39. pmc Beta-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic beta cells
    Noriyuki Sonoda
    Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:6614-9. 2008
    ..Taken together, these studies indicate that beta-arrestin-1 plays a role in GLP-1 signaling leading to insulin secretion, defining a previously undescribed mechanism for GLP-1 action...
  40. pmc Blockade of alpha4 integrin signaling ameliorates the metabolic consequences of high-fat diet-induced obesity
    Chloe C Feral
    Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Diabetes 57:1842-51. 2008
    ..Thus, we hypothesized that mice bearing an alpha4(Y991A) mutation, which blocks signaling, would be protected from development of high-fat diet-induced insulin resistance...
  41. doi request reprint Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance
    Xiaoyong Yang
    Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Nature 451:964-9. 2008
    ..These findings identify a molecular mechanism by which nutritional cues regulate insulin signalling through O-GlcNAc, and underscore the contribution of this modification to the aetiology of insulin resistance and type 2 diabetes...
  42. ncbi request reprint JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity
    Giovanni Solinas
    Department of Medicine, University of Fribourg, Chemin du Musee 5, CH 1700 Fribourg, Switzerland
    Cell Metab 6:386-97. 2007
    ..By contrast, Jnk1 removal from hematopoietic cells has no effect on adiposity but confers protection against HFD-induced insulin resistance by decreasing obesity-induced inflammation...
  43. pmc Selective modulation of promoter recruitment and transcriptional activity of PPARgamma
    DOROTHY D SEARS
    Department of Medicine, University of California, San Diego, 9500 Gilman Drive, MC0673, La Jolla, CA 92093, USA
    Biochem Biophys Res Commun 364:515-21. 2007
    ..Selective modulation of PPARgamma by TZDs resulted in distinct expression profiles and transcription kinetics which may be due to differential promoter activation and chromatin remodeling of target genes...
  44. ncbi request reprint A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways
    M T Audrey Nguyen
    Division of Endocrinology Metabolism, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 282:35279-92. 2007
    ..Together our results show that FFAs can activate CD11c(+) myeloid proinflammatory cells via TLR2/4 and JNK signaling pathways, thereby promoting inflammation and subsequent cellular insulin resistance...
  45. ncbi request reprint Tumor necrosis factor receptor-1 can function through a G alpha q/11-beta-arrestin-1 signaling complex
    Yuji Kawamata
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    J Biol Chem 282:28549-56. 2007
    ....
  46. pmc Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones
    Andrea L Hevener
    Department of Medicine, Division of Endocrinology and Metabolism, UCSD, La Jolla, California, USA
    J Clin Invest 117:1658-69. 2007
    ..These findings reveal an essential role of PPAR gamma in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs...
  47. pmc Myosin 5a is an insulin-stimulated Akt2 (protein kinase Bbeta) substrate modulating GLUT4 vesicle translocation
    Takeshi Yoshizaki
    Department of Medicine 0673, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0673, USA
    Mol Cell Biol 27:5172-83. 2007
    ..Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface...
  48. ncbi request reprint Suppression of PPAR-gamma attenuates insulin-stimulated glucose uptake by affecting both GLUT1 and GLUT4 in 3T3-L1 adipocytes
    Wei Liao
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA
    Am J Physiol Endocrinol Metab 293:E219-27. 2007
    ....
  49. ncbi request reprint Impaired insulin secretion in a mouse model of ataxia telangiectasia
    Philip D Miles
    Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA, USA
    Am J Physiol Endocrinol Metab 293:E70-4. 2007
    ..Our findings support a role for ATM in metabolic function and point toward impaired insulin secretion as the primary cause of DM in A-T...
  50. ncbi request reprint Regulation of receptor tyrosine kinase signaling by GRKs and beta-arrestins
    Christopher J Hupfeld
    Department of Medicine, Division of Endocrinology and Metabolism, University of California San Diego, La Jolla, California 92093, USA
    Annu Rev Physiol 69:561-77. 2007
    ..In this review of RTK signaling, we describe the role of cross talk between RTKs and 7TMRs, focusing specifically on the role played in this process by beta-arrestins and by G proteins...
  51. ncbi request reprint Adenovirus-mediated adiponectin expression augments skeletal muscle insulin sensitivity in male Wistar rats
    Hiroaki Satoh
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0673, USA
    Diabetes 54:1304-13. 2005
    ..These results indicate that chronic adiponectin treatment enhances insulin sensitivity and could serve as a therapy for human insulin resistance...
  52. pmc Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer
    Yaacov Barak
    Gene Expression Laboratory, Howard Hughes Medical Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:303-8. 2002
    ..Together, these observations reveal specific roles for PPARdelta in embryo development and adipocyte physiology, but not cancer...
  53. ncbi request reprint G protein-coupled receptor kinase 2 mediates endothelin-1-induced insulin resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1 pathways in 3T3-L1 adipocytes
    Isao Usui
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    Mol Endocrinol 19:2760-8. 2005
    ....
  54. ncbi request reprint Inhibition of mitochondrial Na+-Ca2+ exchanger increases mitochondrial metabolism and potentiates glucose-stimulated insulin secretion in rat pancreatic islets
    Bumsup Lee
    Division of Metabolic Diseases, MitoKor, San Diego, California 92121, USA
    Diabetes 52:965-73. 2003
    ..These results illustrate the potential utility of agents that affect mitochondrial metabolism as novel insulin secretagogues...
  55. ncbi request reprint Effect of obesity on susceptibility to fatty acid-induced peripheral tissue insulin resistance
    Yolanta T Kruszynska
    Department of Endocrinology and Metabolism, University of California San Diego and the Whittier Institute for Diabetes, La Jolla, CA, USA
    Metabolism 52:233-8. 2003
    ..11, NS). In summary, the effect of a short term elevation of plasma NEFA levels on insulin stimulated GDR and suppression of HGO is comparable in lean and moderately obese subjects...
  56. ncbi request reprint Cdc42 is a Rho GTPase family member that can mediate insulin signaling to glucose transport in 3T3-L1 adipocytes
    Isao Usui
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla 92093, USA
    J Biol Chem 278:13765-74. 2003
    ..Taken together, these data indicate that cdc42 can mediate insulin signaling to GLUT4 translocation and lies downstream of G alpha(q/11) and upstream of PI3-kinase and PKC lambda in this stimulatory pathway...
  57. ncbi request reprint Effect of heterozygous PPARgamma deficiency and TZD treatment on insulin resistance associated with age and high-fat feeding
    Philip D G Miles
    Department of Surgery, University of California, San Diego, USA
    Am J Physiol Endocrinol Metab 284:E618-26. 2003
    ..In conclusion, PPARgamma deficiency partially protects against age-related insulin resistance but does not protect against HF diet-induced insulin resistance...
  58. pmc Beta -Arrestin 1 down-regulation after insulin treatment is associated with supersensitization of beta 2 adrenergic receptor Galpha s signaling in 3T3-L1 adipocytes
    Christopher J Hupfeld
    Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla 92093, USA
    Proc Natl Acad Sci U S A 100:161-6. 2003
    ....
  59. ncbi request reprint Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: implications for insulin resistance
    Hong Ruan
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Diabetes 51:3176-88. 2002
    ..TNF-alpha later alters systemic energy homeostasis that closely resembles the insulin resistance phenotype. Our data suggest that blockade of TNF-alpha action in adipose tissue may prevent TNF-alpha-induced insulin resistance in vivo...
  60. ncbi request reprint The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects
    Joseph G Yu
    Department of Medicine, Division of Endocrinology and Metabolism, University of California San Diego, La Jolla 92093, USA
    Diabetes 51:2968-74. 2002
    ..We have confirmed these results in normal rats. These findings suggest that adiponectin can be regulated by obesity, diabetes, TZDs, and insulin, and it may play a physiologic role in enhancing insulin sensitivity...
  61. pmc Insulin induces heterologous desensitization of G-protein-coupled receptor and insulin-like growth factor I signaling by downregulating beta-arrestin-1
    Stephane Dalle
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    Mol Cell Biol 22:6272-85. 2002
    ....
  62. ncbi request reprint Phosphatidylinositol 3-kinase is required for insulin-stimulated tyrosine phosphorylation of Shc in 3T3-L1 adipocytes
    Satoshi Ugi
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    J Biol Chem 277:18592-7. 2002
    ..2) PI 3-kinase-stimulated generation of membrane phospholipids can localize Shc to the plasma membrane through the Shc PTB domain facilitating phosphorylation by the insulin receptor...
  63. pmc Protein phosphatase 2A forms a molecular complex with Shc and regulates Shc tyrosine phosphorylation and downstream mitogenic signaling
    Satoshi Ugi
    Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California 92093 0673, USA
    Mol Cell Biol 22:2375-87. 2002
    ....
  64. ncbi request reprint GnRH activates ERK1/2 leading to the induction of c-fos and LHbeta protein expression in LbetaT2 cells
    Fujun Liu
    Department of Medicine, University of California, San Diego, California 92093, USA
    Mol Endocrinol 16:419-34. 2002
    ..These results also demonstrate that the nuclear translocation of ERK by GnRH requires PKC signaling...
  65. ncbi request reprint The effects of intracellular calcium depletion on insulin signaling in 3T3-L1 adipocytes
    Dorothy Sears Worrall
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093, USA
    Mol Endocrinol 16:378-89. 2002
    ....
  66. ncbi request reprint Fatty acid-induced insulin resistance: decreased muscle PI3K activation but unchanged Akt phosphorylation
    Yolanta T Kruszynska
    Department of Endocrinology and Metabolism, University of California San Diego, Veterans Administration Center, La Jolla, California 92093, USA
    J Clin Endocrinol Metab 87:226-34. 2002
    ..This in turn may lead to impaired glucose transport through an Akt-independent pathway because Akt phosphorylation was unaffected by elevated NEFA levels...
  67. pmc Insulin-induced GLUT4 translocation involves protein kinase C-lambda-mediated functional coupling between Rab4 and the motor protein kinesin
    Takeshi Imamura
    Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Mol Cell Biol 23:4892-900. 2003
    ....
  68. ncbi request reprint Cellular effects of small molecule PTP1B inhibitors on insulin signaling
    Laiping Xie
    Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 42:12792-804. 2003
    ....
  69. ncbi request reprint Regulation of the insulin receptor by protein kinase C isoenzymes: preferential interaction with beta isoenzymes and interaction with the catalytic domain of betaII
    Tahir S Pillay
    Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0673, USA
    Cell Signal 16:97-104. 2004
    ....
  70. ncbi request reprint Deletion of Gab1 in the liver leads to enhanced glucose tolerance and improved hepatic insulin action
    Emilie A Bard-Chapeau
    Signal Transduction Program, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Med 11:567-71. 2005
    ..Thus, Gab1 acts to attenuate, through promotion of the Erk pathway, insulin-elicited signals flowing through IRS and Akt proteins, which represents a novel balancing mechanism for control of insulin signal strength in the liver...
  71. ncbi request reprint Topiramate is an insulin-sensitizing compound in vivo with direct effects on adipocytes in female ZDF rats
    Jason J Wilkes
    Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, USA
    Am J Physiol Endocrinol Metab 288:E617-24. 2005
    ..Thus the in vivo effects of TPM treatment appear to be exerted through adipose tissue...
  72. ncbi request reprint Insulin-induced beta-arrestin1 Ser-412 phosphorylation is a mechanism for desensitization of ERK activation by Galphai-coupled receptors
    Christopher J Hupfeld
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla 92093, USA
    J Biol Chem 280:1016-23. 2005
    ..These findings provide a new mechanism for insulin-induced desensitization of ERK activation by Galphai-coupled receptors...
  73. ncbi request reprint Mechanism of SHIP-mediated inhibition of insulin- and platelet-derived growth factor-stimulated mitogen-activated protein kinase activity in 3T3-L1 adipocytes
    Prem M Sharma
    Department of Medicine 0673, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0673, USA
    Mol Endocrinol 19:421-30. 2005
    ....
  74. pmc beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1
    Isao Usui
    Department of Medicine 0673, University of California, San Diego, Stein Bldg, Room 210, 9500 Gilman Dr, La Jolla, CA 92093 0673, USA
    Mol Cell Biol 24:8929-37. 2004
    ....
  75. pmc Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes
    Satoshi Ugi
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan
    Mol Cell Biol 24:8778-89. 2004
    ....
  76. pmc Adiposity, dyslipidemia, and insulin resistance in mice with targeted deletion of phospholipid scramblase 3 (PLSCR3)
    Therese Wiedmer
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:13296-301. 2004
    ....
  77. pmc Adenovirus-mediated chronic "hyper-resistinemia" leads to in vivo insulin resistance in normal rats
    Hiroaki Satoh
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla 92093 0673, USA
    J Clin Invest 114:224-31. 2004
    ..Thus elevated resistin levels in normal rats fed a regular chow diet produce many of the features of human syndrome X...
  78. pmc GRK2 is an endogenous protein inhibitor of the insulin signaling pathway for glucose transport stimulation
    Isao Usui
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093 0673, USA
    EMBO J 23:2821-9. 2004
    ..Furthermore, inhibitors of GRK2 can lead to enhanced insulin sensitivity...
  79. ncbi request reprint Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes
    Takeshi Yoshizaki
    Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520 2192, Japan
    J Biol Chem 279:22715-26. 2004
    ..In conclusion, PP2Calpha is a new positive regulator of insulin sensitivity that acts through a direct activation of PI3K in 3T3-L1 adipocytes...
  80. ncbi request reprint Annexin II is a thiazolidinedione-responsive gene involved in insulin-induced glucose transporter isoform 4 translocation in 3T3-L1 adipocytes
    Jie Huang
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego 92093 0673, USA
    Endocrinology 145:1579-86. 2004
    ..In summary, our results show that annexin II is a newly described thiazolidinedione response gene involved in insulin-induced GLUT4 translocation in 3T3-L1 adipocytes...
  81. ncbi request reprint Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity
    Utpal B Pajvani
    Department of Cell Biology, Division of Endocrinology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    J Biol Chem 279:12152-62. 2004
    ..These observations suggest that the HMW adiponectin complex is the active form of this protein, which we directly demonstrate in vivo by its ability to depress serum glucose levels in a dose-dependent manner...
  82. pmc Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle
    Weimin He
    Departments of Medicine and Biology, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 100:15712-7. 2003
    ..These results suggest that syndrome X may be comprised of separable PPARgamma-dependent components whose origins and therapeutic sites may reside in distinct tissues...
  83. pmc Involvement of both G(q/11) and G(s) proteins in gonadotropin-releasing hormone receptor-mediated signaling in L beta T2 cells
    Fujun Liu
    Department of Medicine, University of California, San Diego, California 92093, USA
    J Biol Chem 277:32099-108. 2002
    ..Taken together, these results indicate that the GnRH receptor activates both G(q) and G(s) signaling to regulate gene expression in L beta T2 cells...
  84. ncbi request reprint The effect of oral glucosamine sulfate on insulin sensitivity in human subjects
    Joseph G Yu
    Diabetes Care 26:1941-2. 2003
  85. ncbi request reprint Synthesis and evaluation of photolabile insulin prodrugs
    Lian Sheng Li
    The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 15:3917-20. 2005
    ..Using 2-deoxyglucose uptake assays, both di- and tri-protected compounds were less active than native insulin in the protected state, and showed comparable activity to native insulin upon photoactivation...

Research Grants13

  1. TRAINING PROGRAM IN DIABETES RESEARCH
    Jerrold Olefsky; Fiscal Year: 2007
    ..bring together various activities encompassing the training and education of postdoctoral fellows in the fields of diabetes, metabolism and signal transduction at the University of California, San Diego School of Medicine ..
  2. INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM
    Jerrold Olefsky; Fiscal Year: 2007
    ..abstract_text> ..
  3. Estrogens and Insulin Resistance in Women
    Jerrold Olefsky; Fiscal Year: 2006
    ..abstract_text> ..
  4. Estrogen Effects in Insulin Target and Granulosa Cells
    Jerrold Olefsky; Fiscal Year: 2004
    ..These studies should also highlight the role of inflammatory pathway activation in these pathophysiologic events and this may have potential therapeutic implications for new treatment approaches. ..
  5. INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM
    JERROLD MICHAEL OLEFSKY; Fiscal Year: 2010
    ..These studies should lead to an improved understanding of the basic causes of Type 2 diabetes mellitus and hold the potential for new therapeutic modalities. ..