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Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2005 Dec; Vol. 315 (3), pp. 1396-402. Date of Electronic Publication: 2005 Sep 14. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- 3T3-L1 Cells
Adipocytes metabolism
Animals
Diabetes Mellitus, Experimental blood
Diabetes Mellitus, Experimental metabolism
Dogs
Fasting
Fatty Acids analysis
Fatty Acids metabolism
Glycerol analysis
Glycerol metabolism
Humans
Insulin analysis
Insulin metabolism
Insulin Secretion
Islets of Langerhans metabolism
Lipolysis
Male
Mice
Mice, Inbred BALB C
Rats
Rats, Sprague-Dawley
Rats, Wistar
Species Specificity
Sterol Esterase genetics
Time Factors
Blood Glucose metabolism
Lipids blood
Sterol Esterase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 315
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 16162821
- Full Text :
- https://doi.org/10.1124/jpet.105.086926