Acute exercise reduces insulin resistance-induced TRB3 expression and amelioration of the hepatic production of glucose in the liver of diabetic mice.
TRB3 (a mammalian homolog of Drosophila) is emerging as an important player in the regulation of insulin signaling. TRB3 can directly bind to Ser/Thr protein kinase Akt, the major downstream kinase of insulin signaling. Conversely, physical exercise has been linked to improved glucose homeostasis and enhanced insulin sensitivity; however, the molecular mechanisms by which exercise improves glucose homeostasis, particularly in the hepatic tissue, are only partially known. Here, we demonstrate that acute exercise reduces fasting glucose in two models diabetic mice. Western blot analysis showed that 8 h after a swimming protocol, TRB3 expression was reduced in the hepatic tissue from diet-induced obesity (Swiss) and leptin-deficient (ob/ob) mice, when compared with respective control groups at rest. In parallel, there was an increase in insulin responsiveness in the canonical insulin-signaling pathway in hepatic tissue from DIO and ob/ob mice after exercise. In addition, the PEPCK expression was reduced in the liver after the exercise protocol, suggesting that acute exercise diminished hepatic glucose production through insulin-signaling restoration. Thus, these results provide new insights into the mechanism by which physical activity improves glucose homeostasis in type 2 diabetes.
Lima
Athos F
AF
Universidade Cruzeiro do Sul, Unicsul, São Paulo, SP, Brazil.
Ropelle
Eduardo R
ER
Pauli
José R
JR
Cintra
Dennys E
DE
Frederico
Marisa J S
MJ
Pinho
Ricardo A
RA
Velloso
Lício A
LA
De Souza
Cláudio T
CT
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D004032:Diet; D005215:Fasting; D005947:Glucose / Q000096:biosynthesis*; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D007328:Insulin; C474830:TRB3 protein, mouse; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose