Increased insulin sensitivity and changes in the expression profile of key insulin regulatory genes and beta cell transcription factors in diabetic KKAy-mice after feeding with a soy bean protein rich diet high in isoflavone content.
High content isoflavone soy protein (SBP) (Abalon) has been found in animal studies to possess beneficial effects on a number of the characteristic features of the insulin resistance syndrome. The aim of this study was to investigate whether SBP exerts beneficial effects on metabolism in the diabetic KKAy-mouse. Furthermore, we investigated the long-term in vivo effect of SBP on the expression profile in islets of key insulin regulatory genes. Twenty KKAy-mice, aged 5 weeks, were divided into 2 groups and treated for 9 weeks with either (A) standard chow diet (control) or (B) chow + 50% SBP. Twenty normal C57BL-mice fed with standard chow diet served as nondiabetic controls (C). Blood samples were collected and analyzed before and after intervention. Gene expression was determined in islets by quantitative real-time RT-PCR and Affymetrix microarray. It was demonstrated that long-term treatment with SBP improves glucose homeostasis, increases insulin sensitivity, and lowers plasma triglycerides in diabetic KKAy-mice. SBP reduces fasting plasma glucose, insulin, triglycerides, and total cholesterol. Furthermore, SBP markedly changes the gene expression profile of key insulin regulatory genes GLUT2, GLUT3, Ins1, Ins2, IGF1, Beta2/Neurod1, cholecystokinin, and LDLr, and proliferative genes in islets isolated from KKAy-mice. After 9 weeks of treatment with SBP, plasma glucose and insulin homeostasis was normalized compared to start levels. The results indicate that SBP improves glucose and insulin sensitivity and up-regulates the expression of key insulin regulatory genes.
Nordentoft
I
I
Department of Endocrinology and Metabolism C, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark. Iver.Nordentoft@ki.au.dk
Jeppesen
P B
PB
Hong
J
J
Abudula
R
R
Hermansen
K
K
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004032:Diet; D020869:Gene Expression Profiling; D007328:Insulin / Q000097:blood / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000737:chemistry*; D007529:Isoflavones / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D030262:Soybean Proteins / Q000008:administration & dosage*; D014157:Transcription Factors / Q000032:analysis*
D001786:Blood Glucose; D007328:Insulin; D007529:Isoflavones; D008055:Lipids; D030262:Soybean Proteins; D014157:Transcription Factors