Impact of hyperglycemic control on left ventricular myocardium. A molecular and cellular basic study in a diabetic rat model

Int Heart J. 2009 Mar;50(2):191-206. doi: 10.1536/ihj.50.191.

Abstract

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).

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Connexin 43 / genetics
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism*
  • Disease Models, Animal
  • Endothelin-1 / biosynthesis
  • Endothelin-1 / drug effects
  • Heart Ventricles / metabolism*
  • Hemoglobin A / biosynthesis
  • Hemoglobin A / drug effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / pharmacology
  • Insulin / therapeutic use*
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Myocardium / metabolism*
  • Nitric Oxide Synthase Type III / biosynthesis
  • Nitric Oxide Synthase Type III / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Protein Kinase C-epsilon / deficiency
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / deficiency
  • Ventricular Function, Left / drug effects*

Substances

  • Connexin 43
  • Endothelin-1
  • Hypoglycemic Agents
  • Insulin
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • RNA, Messenger
  • RNA-Binding Proteins
  • Transcription Factors
  • Hemoglobin A
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Protein Kinase C-epsilon
  • Matrix Metalloproteinase 9