Glycolytic enzyme expression and pyruvate kinase activity in cultured fibroblasts from type 1 diabetic patients with

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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

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Elisabetta Iori1, Renato Millioni, Lucia Puricelli

  • 1Department of Clinical and Experimental Medicine, Chair of Metabolism, 35128 Padova, Italy.

Biochimica Et Biophysica Acta
|October 9, 2008
PubMed

Insights

Type 1 diabetes mellitus with kidney disease shows altered glucose metabolism enzymes in skin cells. These changes in glycolytic enzymes may contribute to insulin resistance and kidney damage in patients.

Area of Science:

  • Biochemistry
  • Metabolic Disorders
  • Diabetology

Background:

  • Type 1 diabetes mellitus (T1DM) patients with nephropathy (DN+) exhibit insulin resistance.
  • Understanding molecular alterations in glucose metabolism is crucial for T1DM(DN+) pathophysiology.

Purpose of the Study:

  • To identify novel molecular targets in glucose metabolism alterations in T1DM(DN+) patients.
  • To compare glycolytic enzyme expression and pyruvate kinase activity in T1DM(DN+) versus T1DM(DN-) and control fibroblasts.

Main Methods:

  • Cultured human skin fibroblasts from T1DM(DN+) and T1DM(DN-) patients and controls.
  • Gene expression analysis via cRNA microarray.
  • Protein expression analysis using 2D electrophoresis and mass spectrometry.
  • Pyruvate kinase activity assay.

Main Results:

  • Increased gene expression of hexokinase, phosphoglucomutase, phosphofructokinase, aldolase, and triosephosphate isomerase in T1DM(DN+) fibroblasts compared to controls.
  • Altered protein expression of triosephosphate isomerase, enolase, and pyruvate kinase in T1DM(DN+) fibroblasts.
  • Lower pyruvate kinase activity in T1DM(DN+) fibroblasts compared to T1DM(DN-) and control fibroblasts.

Conclusions:

  • Novel alterations in glycolytic enzymes are identified in T1DM(DN+) patients.
  • These metabolic changes may be linked to insulin resistance and renal damage in T1DM(DN+).
  • Fibroblast analysis provides insights into systemic metabolic dysregulation in diabetic nephropathy.

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