, a bio/informatics shared resource is still "open for business" - Visit the CDS website

Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis.

Brissova M, Blaha M, Spear C, Nicholson W, Radhika A, Shiota M, Charron MJ, Wright CV, Powers AC
Am J Physiol Endocrinol Metab. 2005 288 (4): E707-14

PMID: 15562255 · DOI:10.1152/ajpendo.00252.2004

In type 2 diabetes mellitus, insulin resistance and an inadequate pancreatic beta-cell response to the demands of insulin resistance lead to impaired insulin secretion and hyperglycemia. Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. To investigate the role of PDX-1 in islet compensation for insulin resistance, we examined glucose disposal, insulin secretion, and islet cell mass in mice of four different genotypes: wild-type mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/-;PDX-1+/-). The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged glucose clearance. GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content. These results indicate that PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the beta-cell's compensatory response to insulin resistance, impairs glucose homeostasis, and may contribute to the pathogenesis of type 2 diabetes.

MeSH Terms (22)

Age Factors Animals Blood Glucose Blotting, Western Diabetes Mellitus, Type 2 Gene Silencing Glucose Tolerance Test Glucose Transporter Type 4 Heterozygote Homeodomain Proteins Homeostasis Insulin Resistance Islets of Langerhans Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Fluorescence Monosaccharide Transport Proteins Muscle Proteins Organ Size Statistics, Nonparametric Trans-Activators

Connections (4)

This publication is referenced by other Labnodes entities: