Myocardial Insulin Signaling and Glucose Transport Are Up-regulated in Goto–Kakizaki Type 2 Diabetic Rats After Ileal Transposition

Abstract

Ileal transposition (IT) as one of the effective treatments for non-obese type 2 diabetes mellitus has been widely investigated. However, the mechanisms underlying profound improvements in glucose homeostasis are still uncertain. Our objective was to explore the myocardial insulin signal transduction and glucose disposal in non-obese type 2 diabetes mellitus rats after IT surgery. Adult male Goto-Kakizaki (GK) rats or Sprague-Dawley (SD) rats were randomly assigned to diabetic IT, diabetic sham-IT, and non-diabetic control SD groups. Food intake, body weight, fasting plasma glucose, insulin tolerance, and serum glucagon-like peptide-1 (GLP-1) were measured. Subsequently, the myocardial glucose uptake and the protein levels of insulin receptor-beta (IR-β), phosphorylated IR-β, insulin receptor substrate 1 (IRS-1), phosphorylated IRS-1, and IRS-1-associated phosphatidylinositol-3 kinase (PI3K) from myocardial cell lysates were evaluated. We also assessed the expression of glucose transporter 4 (GLUT4) in both skeletal muscle and myocardial cell lysates. Compared to sham operations within 6months, IT surgery for GK rats did (1) result in less food intake and reduced body weight gain over time, (2) improve plasma glucose homeostasis with increased serum GLP-1 secretion and myocardial glucose uptake, (3) increase protein expression of insulin signaling pathway, including IR-β, IRS-1 and their phosphorylation levels, and IRS-1-associated PI3K in the myocardium, and (4) enhance the protein levels of membrane GLUT4 in skeletal muscle and myocardium. IT surgery ameliorates glucose disorder in GK type 2 diabetic rats. Meanwhile, IT surgery is effective in up-regulating both myocardial insulin signaling and glucose disposal within 6months.