Evidence of impaired adipogenesis in insulin resistance

• To elucidate the roles of adipose tissue and skeletal muscle in the early development of insulin resistance, we characterized gene expression profiles of isolated adipose cells and skeletal muscle of non-diabetic insulin-resistant first-degree relatives of type 2 diabetic patients using oligonucleotide microarrays. About 600 genes and expressed sequence tags, which displayed a gene expression pattern of cell proliferation, were differentially expressed in the adipose cells. The differentially expressed genes in the skeletal muscle were mostly related to the cellular signal transduction and transcriptional regulation. To verify the microarray findings, we studied expression of genes participating in adipogenesis. The expression of Wnt signaling genes, WNT1, FZD1, DVL1, GSK3beta, beta-catenin, and TCF1, and adipogenic transcription factors, C/EBPalpha and beta and delta, PPARgamma, and SREBP-1, was reduced in the adipose tissue. The expression of adipose-specific proteins related to terminal differentiation, such as adiponectin and aP2, was reduced both in the adipose tissue and in the adipose cells isolated from portions of the biopsies. The adipose cells were enlarged in the insulin-resistant relatives and the cell size inversely correlated with the expression of the Wnt signaling genes, adiponectin, and aP2. Our findings suggest that insulin resistance is associated with an impaired adipogenesis.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Adipocytes/*metabolism/physiology

Adipose Tissue/cytology/*metabolism

Adult

Case-Control Studies

Cell Size

Cytoskeletal Proteins/biosynthesis

DNA-Binding Proteins/metabolism

Diabetes Mellitus

Type 2/genetics/metabolism

Family Health

Gene Expression Profiling

Glycogen Synthase Kinase 3/metabolism

Humans

Insulin Resistance/*physiology

Lymphoid Enhancer-Binding Factor 1

Male

Middle Aged

Muscle

Skeletal/metabolism/physiology

Oligonucleotide Array Sequence Analysis

Proto-Oncogene Proteins/genetics/metabolism

Regression Analysis

Signal Transduction

T Cell Transcription Factor 1

Trans-Activators/biosynthesis

Transcription Factors/metabolism

Wnt Proteins

Wnt1 Protein

*Zebrafish Proteins

beta Catenin

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)