Impact of hyperglycemic control on left ventricular myocardium. A molecular and cellular basic study in a diabetic rat model.
This experimental study investigated the impact of hyperglycemic control on left ventricular (LV) function using a model of diabetes mellitus (DM) (induced by streptozocin 60 mg/kg). Sixteen adult-Sprague Dawley rats were divided into group 1 (poor hyperglycemic control, n = 8) and group 2 (good hyperglycemic control, n = 8). Diabetic rats and 8 healthy rats serving as controls (group 3) were sacrificed on day 28 after DM induction. The results demonstrated that HbA(1C) on day 28 was higher in group 1 than in groups 2 and 3 (P < 0.0001). The mRNA expressions of MMP-9 and endothelin-1 were elevated in group 1 compared with that in groups 2 and 3 (P < 0.05), whereas PGC-1alpha and eNOS were lower in group 1 than in groups 2 and 3 (P < 0.05). The number of apoptotic nuclei was higher in group 1 than in groups 2 and 3 (P < 0.01). The integrated area (microm(2)) of connexin43 (Cx43), Cx43 protein expression, and LV function were lower in group 1 than in groups 2 and 3 (P < 0.05). Moreover, PKC-epsilon expression in the mitochondrial compartment was decreased in group 1 compared to that in groups 2 and 3 (P < 0.005).
Sung
Pei-Hsun
PH
Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Sun
Cheuk-Kwan
CK
Ko
Sheung-Fat
SF
Chang
Li-Teh
LT
Sheu
Jiunn-Jye
JJ
Lee
Fan-Yen
FY
Wu
Chiung-Jen
CJ
Chua
Sarah
S
Yip
Hon-Kan
HK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism*; D006441:Hemoglobin A / Q000096:biosynthesis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051744:Protein Kinase C-epsilon / Q000172:deficiency; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000172:deficiency; D016277:Ventricular Function, Left / Q000187:drug effects*
D018031:Connexin 43; D019332:Endothelin-1; D007004:Hypoglycemic Agents; D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D006441:Hemoglobin A; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051744:Protein Kinase C-epsilon; D020780:Matrix Metalloproteinase 9