PMID- 16757548 OWN - NLM STAT- MEDLINE DCOM- 20061121 LR - 20181201 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 291 IP - 5 DP - 2006 Nov TI - Tissue-specific expression and regulation of GSK-3 in human skeletal muscle and adipose tissue. PG - E891-8 AB - Glycogen synthase kinase-3 (GSK-3) is a ubiquitous kinase implicated in both insulin action and adipogenesis. To determine how these multiple roles may relate to insulin resistance, we studied the regulation of GSK-3 protein expression and phosphorylation in skeletal muscle and isolated adipocytes from nonobese healthy control (HC), obese control (OC), and obese type 2 diabetic (OT2D) subjects. At baseline there were no differences in the GSK-3 protein expression in adipocytes. OC subjects underwent a 6-mo caloric restriction resulting in a 7% decrease in body mass index (BMI) and a 21% improvement in insulin-stimulated whole body glucose disposal rate (GDR). GSK-3alpha and GSK-3beta expression decreased in adipocytes (P < 0.05), whereas GSK-3alpha protein expression increased in skeletal muscle (P < 0.05). OT2D subjects were treated with troglitazone or metformin for 3-4 mo. After troglitazone treatment GDR improved (P < 0.05) despite an increase in BMI (P < 0.05), whereas metformin had no significant effect on GDR. There was no significant change in GSK-3 expression in adipocytes following troglitazone, whereas both GSK-3alpha and -beta were decreased in skeletal muscle (P < 0.05). Metformin treatment had no significant impact on GSK-3 protein expression in either adipocytes or skeletal muscle. Neither treatment influenced GSK-3 serine phosphorylation in skeletal muscle or adipocytes. These results suggest that there is tissue specificity for the regulation of GSK-3 in humans. In skeletal muscle GSK-3 plays a role in control of metabolism and insulin action, whereas the function in adipose tissue is less clear. FAU - Ciaraldi, Theodore P AU - Ciaraldi TP AD - Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA. FAU - Oh, Deborah K AU - Oh DK FAU - Christiansen, Louis AU - Christiansen L FAU - Nikoulina, Svetlana E AU - Nikoulina SE FAU - Kong, Alice P S AU - Kong AP FAU - Baxi, Sunita AU - Baxi S FAU - Mudaliar, Sunder AU - Mudaliar S FAU - Henry, Robert R AU - Henry RR LA - eng GR - M01-RR-00827/RR/NCRR NIH HHS/United States GR - R01-DK-258291/DK/NIDDK NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20060606 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Blood Glucose) RN - 0 (Chromans) RN - 0 (Hypoglycemic Agents) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - EC 2.7.11.1 (GSK3B protein, human) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) RN - EC 2.7.11.26 (glycogen synthase kinase 3 alpha) RN - I66ZZ0ZN0E (Troglitazone) SB - IM MH - Adult MH - Aged MH - Biopsy MH - Blood Glucose/metabolism MH - Caloric Restriction MH - Chromans/administration & dosage MH - Diabetes Mellitus, Type 2/drug therapy/*metabolism MH - Female MH - Glycogen Synthase Kinase 3/*metabolism MH - Glycogen Synthase Kinase 3 beta MH - Humans MH - Hypoglycemic Agents/administration & dosage MH - Insulin Resistance MH - Male MH - Metformin/administration & dosage MH - Middle Aged MH - Muscle, Skeletal/cytology/*enzymology MH - Obesity/drug therapy/metabolism MH - Phosphorylation MH - Subcutaneous Fat/cytology/*enzymology MH - Thiazolidinediones/administration & dosage MH - Troglitazone MH - Weight Loss EDAT- 2006/06/08 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/06/08 09:00 PHST- 2006/06/08 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/06/08 09:00 [entrez] AID - 00176.2006 [pii] AID - 10.1152/ajpendo.00176.2006 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E891-8. doi: 10.1152/ajpendo.00176.2006. Epub 2006 Jun 6.