The rapid onset of hyperglycaemia in ZDF rats was associated with a widespread alteration of metabolic proteins implicated in glucose metabolism in the heart.
The present study tested the hypothesis that the phosphorylation and regulation of metabolic proteins implicated in glucose homeostasis were impaired in the heart of the type 2 diabetic Zucker-diabetic-fatty (ZDF) rat model. The onset of hyperglycaemia in ZDF rats was not uniform, instead it either progressed rapidly (3-4 weeks) or was delayed (6-8 weeks). In both the early and late onset hyperglycaemic ZDF rats, AMPKalpha Thr172 phosphorylation in the heart was significantly decreased. In the early onset hyperglycaemic ZDF rats, PKB Ser473 phosphorylation was reduced, whereas Thr308 phosphorylation was significantly increased. In the late onset hyperglycaemic ZDF rats, PKB Ser473 phosphorylation was unchanged, but Thr308 phosphorylation remained elevated. Cardiac GLUT4 protein and mRNA expression were significantly reduced in the early onset hyperglycaemic ZDF rats, whereas increased protein expression was observed in the late onset hyperglycaemic ZDF rats. In conclusion, the present study has demonstrated that following a more rapid onset of hyperglycaemia, the type 2 diabetic heart is more prone to alterations in the signaling proteins implicated in glucose metabolism.
Lajoie
Claude
C
Department of Human Kinetics, Laurentian University, Ramsey Lake Road, ON P3E 2C6, Canada. Claude_Lajoie@UQAC.ca
Béliveau
Louise
L
Trudeau
François
F
Lavoie
Nathalie
N
Massicotte
Guy
G
Gagnon
Sylvain
S
Calderone
Angelino
A
D055372:AMP-Activated Protein Kinases; D000818:Animals; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009097:Multienzyme Complexes; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D006003:Glycogen; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases; D005947:Glucose