Details

Autor(en) / Beteiligte

• Carlson, Edward
• Bleth, Jordan
• Miller, Cory
• Laturnus, Donna
• Young, Laurie Kim
• Schaff, Elizabeth

Titel

Is Diabetic Glomerular Basement Membrane Thickening Hyperglycemia Driven? Or Is It a Part of the Normal Aging Process

Ist Teil von

• The FASEB journal, 2016-04, Vol.30 (S1)

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Abstract only Most microvascular basement membranes, including glomerular basement membranes (GBMs) are thickened in diabetes, and though the molecular mechanisms are elusive, hyperglycemia is nearly universally believed to play a major role. However, we and others have also shown that GBMs thicken with age, and in at least one spontaneous diabetic animal model (BB Wistar rats), GBMs thicken beyond normal age‐related thickening in the absence of hyperglycemia. Accordingly, in the current study, electron microscopic morphometric techniques were employed to determine whether age‐related or glycemia‐related GBM thickening may be the dominant parameter. Four murine genotypes including 150‐ and 450‐day‐old FVB background (normoglycemic), NMT, (transgenic normoglycemic), OVE (hyperglycemic), and OVE‐NMT (transgenic hyperglycemic) were prepared for TEM examination and determination of true GBM thickness by the “gold standard”, orthogonal intercept technique. Our data indicated that for age‐matched animals, increased glycemic level was a consistent predictor of increased GBM thickness. As examples, GBMs from both 150‐ and 450‐day‐old diabetic mice were approximately 24% thicker than age‐matched normoglycemic animals. Although these data strongly suggest that glycemia is an important parameter in GBM thickening, our unbiased morphometric analyses also show that regardless of blood sugar levels (including normoglycemics), substantially increased (88–100%) GBM thickening is recapitulated in 450‐day animals compared to glycemia‐matched 150‐day‐old mice. Likewise, numerous other cellular and extracellular parameters are augmented by increased duration, and are amplified further by glycemic levels. Alternatively, these parameters may be diminished by curtailed time and/or mitigated by reduced oxidative stress. In summary, both time and level of glycemia are major factors in early GBM thickening, and both must be considered in any therapeutic intervention in the progression of diabetic or non‐diabetic basement membrane disease.