BIOSIS / 2006:93908

AN

    2006:93908  BIOSIS

DN

    PREV200600097036

TI

    Specific inhibition of hormone-sensitive lipase improves lipid
    profile while reducing plasma glucose. 

AU

    Claus, Thomas H.; Lowe, Derek B.; Liang, Yin; Salhanick, Arthur I.; Keiper
    Lubeski, Christine; Yang, Ling; Lemoine, Lynn; Zhu, Jian; Clairmont, Kevin
    B. [Reprint Author]

CS

    Bayer Res Ctr, Dept Metab Disorders Res, 400 Morgan Lane, West Haven, CT
    06516 USA
    kevin.clairmont.b@bayer.com

SO

    Journal of Pharmacology and Experimental Therapeutics, (DEC 2005) Vol.
    315, No. 3, pp. 1396-1402. http://www.jpet.org. 
    CODEN: JPETAB. ISSN: 0022-3565. 

DT

    Article

LA

    English

ED

    Entered STN: 1 Feb 2006
    Last Updated on STN: 1 Feb 2006

AB

    Elevation of plasma free fatty acids has been linked with insulin
    resistance and diabetes.  Inhibition of lipolysis may provide a
    mechanism to decrease plasma fatty acids, thereby improving insulin
    sensitivity.  Hormone-sensitive lipase (HSL) is a critical enzyme
    involved in the hormonally regulated release of fatty acids and glycerol
    from adipocyte lipid stores, and its inhibition may thus improve insulin
    sensitivity and blood glucose handling in type 2 diabetes.  In rat
    adipocytes, forskolin-activated lipolysis was blocked by in vitro addition
    of a potent and selective HSL inhibitor or by prior treatment of the
    animals themselves.  Antilipolytic effects also were demonstrated in
    overnight-fasted mice, rats, and dogs with species-dependent effects on
    plasma free fatty acid levels but with similar reductions in plasma
    glycerol being observed in all species.  Inhibition of HSL also reduced
    hyperglycemia in streptozotocin-induced diabetic rats.  The data support
    a connection between adipose tissue lipolysis and plasma glucose levels.

CC

    Cytology - Animal   02506
    Biochemistry studies - General   10060
    Biochemistry studies - Carbohydrates   10068
    Enzymes - General and comparative studies: coenzymes   10802
    Pathology - Therapy   12512
    Metabolism - Metabolic disorders   13020
    Blood - Blood and lymph studies   15002
    Blood - Blood cell studies   15004
    Endocrine - General   17002
    Endocrine - Pancreas   17008
    Pharmacology - General   22002
    Toxicology - General and methods   22501

IT

    Major Concepts
       Pharmacology; Enzymology (Biochemistry and Molecular Biophysics);
       Endocrine System (Chemical Coordination and Homeostasis)

IT

    Parts, Structures, & Systems of Organisms
       plasma: blood and lymphatics

IT

    Diseases
       insulin resistance syndrome: endocrine disease/pancreas, metabolic
       disease
       Insulin Resistance (MeSH)

IT

    Diseases
       type 2 diabetes: endocrine disease/pancreas, metabolic disease, drug
       therapy, chemically-induced
       Diabetes Mellitus, Non-Insulin-Dependent (MeSH)

IT

    Chemicals & Biochemicals
       glucose; glycerol; streptozotocin; hormone-sensitive lipase:
       inhibition; hormone-sensitive lipase inhibitor: enzyme inhibitor-drug

ORGN

    Classifier
       Canidae   85765
    Super Taxa
       Carnivora; Mammalia; Vertebrata; Chordata; Animalia
    Organism Name
       dog (common): breed-beagle, male
    Taxa Notes
       Animals, Carnivores, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman
       Mammals, Vertebrates

ORGN

    Classifier
       Muridae   86375
    Super Taxa
       Rodentia; Mammalia; Vertebrata; Chordata; Animalia
    Organism Name
       Wistar rat (common): male
       rat (common): strain-Sprague-Dawley, male
       mouse (common): strain-Balb/C, male
       3T3-L1 cell line (cell_line): murine adipocyte cells
    Taxa Notes
       Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals,
       Rodents, Vertebrates

RN

    58367-01-4 (glucose)
    56-81-5 (glycerol)
    18883-66-4 (streptozotocin)
    9001-62-1 (hormone-sensitive lipase)