Tissue-specific expression and regulation of GSK-3 in human skeletal muscle and adipose tissue.
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.
Ciaraldi
Theodore P
TP
Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
Oh
Deborah K
DK
Christiansen
Louis
L
Nikoulina
Svetlana E
SE
Kong
Alice P S
AP
Baxi
Sunita
S
Mudaliar
Sunder
S
Henry
Robert R
RR
D000328:Adult; D000368:Aged; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D002839:Chromans / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D010766:Phosphorylation; D050151:Subcutaneous Fat / Q000166:cytology / Q000201:enzymology*; D045162:Thiazolidinediones / Q000008:administration & dosage; D000077288:Troglitazone; D015431:Weight Loss
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D000077288:Troglitazone