Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells.
Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-gamma) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-gamma activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-gamma in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.
Lopez
Veronica
V
Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262, USA.
Saraff
Kumuda
K
Medh
Jheem D
JD
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors* / Q000235:genetics; D032342:Muscle Cells / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D047495:PPAR gamma / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D008071:Lipoprotein Lipase; D005947:Glucose; C039671:ciglitazone
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