The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 11 17a
Copyright © 2005 by The Endocrine Society
Endocrinology & Metabolism News November 2005
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Endocrine Discovery
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Long-term (30-year) risks of becoming overweight and obese were greater than 50% and 25%, respectively, among 4,117 Framingham Heart Study participants.
(Ann Intern Med (Oct. 4, 2005) 143(7):473)
A high-normal fasting plasma glucose (
87 mg/dL) was an independent risk factor for type 2 diabetes among 13,163 healthy younger men, as was the combination of a glucose 91–99 mg/dL and either high-normal triglyceride level (150 mg/dL) or BMI (30).
(N Engl J Med (Oct. 6, 2005) 353(14):1454)
Magnetic nanoparticle MRI permitted noninvasive visualization of pancreatic microvascular leakage reflecting inflammation in a murine model of type 1 diabetes, and demonstrating its reversal by an anti-CD3 monoclonal antibody therapy.
(J Clin Invest (Sept. 1, 2005) 115(9):2454)
Megalin, a cell surface receptor in reproductive tissues, facilitated endocytosis of sex steroids bound to plasma proteins, with subsequent intracellular release of estrogens and androgens for nuclear receptor interactions and the recycling of binding proteins. Megalin knockout mice manifested impaired sexual development.
(Cell (Sept. 9, 2005) 122(5):751)
Lysine-specific demethylase 1 (LSD1) promoted androgen-receptor-dependent transcription by interacting with the androgen receptor to form chromatin-associated complexes that demethylated histone marks and relieved repression of specific genes.
(Nature (Sept. 15, 2005) 437:436)[Medline]
Overexpression of the protein hormone Klotho extended the murine lifespan by binding to cell surface receptor and repressing insulin and IGF-1 signaling. Furthermore, the aging phenotype seen in Klotho deficient mice was mimicked by interfering with insulin and IGF-1 signaling.
(Science (Sept. 16, 2005) 309:1829)[Abstract/Free Full Text]
Activation of orexin neurons in the lateral hypothalamus restored extinguished drug-seeking behavior, as did direct delivery of orexin A into the ventral tegmental area—findings suggesting a role for these neurons in reward-seeking, drug relapse and addiction.
(Nature (Sept. 22) 437:556)
In adipocytes, a chronically elevated insulin level prevented ß-adrenergic receptor-mediated activation of protein kinase A, an effect that was mimicked by disrupting PKA scaffolding. These findings suggest that alteration of the close spatial relationship of the ß-adrenergic receptor and PKA represents a new mechanism for heterologous signaling pathway transduction.
(Nature (Sept. 22) 437:569)
Myocardial infarct size, myocardiocyte apoptosis and tumor necrosis factor (TNF)-
expression after ischemia-reperfusion were increased in adiponectin-deficient mice, and adiponectin administration reduced all of these effects. Additional studies suggested that the protective effects of adiponectin were mediated by both AMP-activated protein kinase- and COX-2–dependent mechanisms.
(Nat Med (Oct. 2005) 11:1096)[CrossRef][Medline]
Inhibition of cyclin-dependent kinase 5 (Cdk5) activity augmented insulin secretion by MIN6 cells and pancreatic islets in the presence of high but not low glucose concentrations—suggesting Cdk5 and its activator p35 might be novel targets to enhance glucose-stimulated insulin secretion.
(Nat Med (Oct. 2005) 11:1104)[CrossRef][Medline]
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Endocrine Practice
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The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended approval of the dual /
PPAR activator, muraglitazar (PargluvaTM) to treat type 2 diabetes, as monotherapy or combined with metformin. In addition to its PPAR-mediated hypoglycemic action, the additional PPAR action lowers triglyceride and elevates HDL levels. (For more information, see: www.bms.com/news/press/data/fg_press_release_5831.html.)
The American Diabetes Association and the European Association for the Study of Diabetes questioned whether metabolic syndrome should actually be considered a syndrome, noting that it "has been imprecisely defined, there is a lack of certainty regarding its pathogenesis, and ... considerable doubt regarding its value as a CVD risk marker." In a joint publication, the societies concluded that "clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the ‘metabolic syndrome.’"
(Diabetologia (September 2005) 48(9):1684)
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Endocrine Education & Training
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The ACP, AAMC, and American Medical Student Association highlighted their concern about medical student debt and its distortion of career choices at a Capitol Hill conference—noting that typical students from public and private schools may be as much as $100,000 and $135,000, respectively, in debt, with 25% owing more than $150,000. (For more information, visit: http://www.amsa.org/meded/studentdebtsummit.cfm)
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Milestones in Endocrinology
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90 years ago, Walter B. Cannon published his classic book Bodily Changes in Pain, Hunger, Fear and Rage, in which he correlated physical responses of the endocrine organs and sympathetic nervous system to social stimuli.
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In the Journal 25 Years Ago
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Pregnancies following chronic intermittent (pulsatile) administration of Gn-RH by means of a portable pump—a new approach to the treatment of infertility in hypothalamic amenorrhea. Leyendecker G, Wildt L, Hansmann M.
J Clin Endocrinol Metab 1980;51:1214–1216.[Abstract]
"It is the purpose of this communication to present chronic intermittent administration of Gn-RH via an automated pump as a new method of treatment of hypothalamic amenorrhea and to describe the first two successful inductions of pregnancy with this method..."
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Endocrinologists
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Stuart Brink has been chosen as president-elect of the International Society for Pediatric and Adolescent Diabetes.
Linda Giudice has become Chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of California-San Francisco School of Medicine.
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Footnotes
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Readers are encouraged to suggest items for Endocrinology and Metabolism News by email (sherman@endo-society.org). Submissions will be considered based on their significance and timeliness.
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