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)