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<p><b>New page</b></p><div>AN <br />
2006:93908 BIOSIS<br />
DN <br />
PREV200600097036<br />
TI <br />
Specific inhibition of hormone-sensitive lipase improves lipid<br />
profile while reducing plasma glucose. <br />
AU <br />
Claus, Thomas H.; Lowe, Derek B.; Liang, Yin; Salhanick, Arthur I.; Keiper<br />
Lubeski, Christine; Yang, Ling; Lemoine, Lynn; Zhu, Jian; Clairmont, Kevin<br />
B. [Reprint Author]<br />
CS <br />
Bayer Res Ctr, Dept Metab Disorders Res, 400 Morgan Lane, West Haven, CT<br />
06516 USA<br />
kevin.clairmont.b@bayer.com<br />
SO <br />
Journal of Pharmacology and Experimental Therapeutics, (DEC 2005) Vol.<br />
315, No. 3, pp. 1396-1402. http://www.jpet.org. <br />
CODEN: JPETAB. ISSN: 0022-3565. <br />
DT <br />
Article<br />
LA <br />
English<br />
ED <br />
Entered STN: 1 Feb 2006<br />
Last Updated on STN: 1 Feb 2006<br />
AB <br />
Elevation of plasma free fatty acids has been linked with insulin<br />
resistance and diabetes. Inhibition of lipolysis may provide a<br />
mechanism to decrease plasma fatty acids, thereby improving insulin<br />
sensitivity. Hormone-sensitive lipase (HSL) is a critical enzyme<br />
involved in the hormonally regulated release of fatty acids and glycerol<br />
from adipocyte lipid stores, and its inhibition may thus improve insulin<br />
sensitivity and blood glucose handling in type 2 diabetes. In rat<br />
adipocytes, forskolin-activated lipolysis was blocked by in vitro addition<br />
of a potent and selective HSL inhibitor or by prior treatment of the<br />
animals themselves. Antilipolytic effects also were demonstrated in<br />
overnight-fasted mice, rats, and dogs with species-dependent effects on<br />
plasma free fatty acid levels but with similar reductions in plasma<br />
glycerol being observed in all species. Inhibition of HSL also reduced<br />
hyperglycemia in streptozotocin-induced diabetic rats. The data support<br />
a connection between adipose tissue lipolysis and plasma glucose levels.<br />
CC <br />
Cytology - Animal 02506<br />
Biochemistry studies - General 10060<br />
Biochemistry studies - Carbohydrates 10068<br />
Enzymes - General and comparative studies: coenzymes 10802<br />
Pathology - Therapy 12512<br />
Metabolism - Metabolic disorders 13020<br />
Blood - Blood and lymph studies 15002<br />
Blood - Blood cell studies 15004<br />
Endocrine - General 17002<br />
Endocrine - Pancreas 17008<br />
Pharmacology - General 22002<br />
Toxicology - General and methods 22501<br />
IT <br />
Major Concepts<br />
Pharmacology; Enzymology (Biochemistry and Molecular Biophysics);<br />
Endocrine System (Chemical Coordination and Homeostasis)<br />
IT <br />
Parts, Structures, & Systems of Organisms<br />
plasma: blood and lymphatics<br />
IT <br />
Diseases<br />
insulin resistance syndrome: endocrine disease/pancreas, metabolic<br />
disease<br />
Insulin Resistance (MeSH)<br />
IT <br />
Diseases<br />
type 2 diabetes: endocrine disease/pancreas, metabolic disease, drug<br />
therapy, chemically-induced<br />
Diabetes Mellitus, Non-Insulin-Dependent (MeSH)<br />
IT <br />
Chemicals & Biochemicals<br />
glucose; glycerol; streptozotocin; hormone-sensitive lipase:<br />
inhibition; hormone-sensitive lipase inhibitor: enzyme inhibitor-drug<br />
ORGN <br />
Classifier<br />
Canidae 85765<br />
Super Taxa<br />
Carnivora; Mammalia; Vertebrata; Chordata; Animalia<br />
Organism Name<br />
dog (common): breed-beagle, male<br />
Taxa Notes<br />
Animals, Carnivores, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman<br />
Mammals, Vertebrates<br />
ORGN <br />
Classifier<br />
Muridae 86375<br />
Super Taxa<br />
Rodentia; Mammalia; Vertebrata; Chordata; Animalia<br />
Organism Name<br />
Wistar rat (common): male<br />
rat (common): strain-Sprague-Dawley, male<br />
mouse (common): strain-Balb/C, male<br />
3T3-L1 cell line (cell_line): murine adipocyte cells<br />
Taxa Notes<br />
Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals,<br />
Rodents, Vertebrates<br />
RN <br />
58367-01-4 (glucose)<br />
56-81-5 (glycerol)<br />
18883-66-4 (streptozotocin)<br />
9001-62-1 (hormone-sensitive lipase)</div>
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