PURPOSE: To determine whether tight glycemic control prevents development of basement membrane (BM) thickening in retinal and glomerular capillaries of diabetic rats and whether the extent to which BM thickening develops is linked to fibronectin (FN) overexpression and the degree of hyperglycemia. METHODS: Retinal and renal cortical tissues obtained from the tightly controlled diabetic (TC), poorly controlled diabetic (D), and nondiabetic (N) control rats were subjected to morphometric and biochemical analyses. In both tissues, capillary BM thickening was determined by electron microscopy, and FN protein level was assessed by Western blot analysis. Routine measurements of blood glucose level and glycohemoglobin level were performed throughout the study. RESULTS: The HbA1c level was significantly increased in D rats, but not in TC rats, compared with those of the N rats with a concomitant increase in capillary BM thickness and FN protein expression in retinal and renal tissues. A strong correlation was observed between retinal and glomerular capillary BM thickness (r=0.79, P=0.0001), between retinal and kidney FN protein levels (r=0.7, P=0.005), between HbA1c and FN protein levels in the retina (r=0.66, P=0.006) and kidney (r= .84, P=0.0003), and between HbA1c level and BM thickness in retinal (r=0.76, P=0.0002) and renal tissues (r=0.64, P=0.004). CONCLUSIONS: In diabetes BM thickening develops in retinal and glomerular capillaries in a correlated manner. Tight glycemic control may be beneficial in preventing the pathologic development of capillary BM thickening and FN overexpression in retinal and renal tissues, two target tissues of diabetic microangiopathy.
PURPOSE: To determine whether tight glycemic control prevents development of basement membrane (BM) thickening in retinal and glomerular capillaries of diabeticrats and whether the extent to which BM thickening develops is linked to fibronectin (FN) overexpression and the degree of hyperglycemia. METHODS: Retinal and renal cortical tissues obtained from the tightly controlled diabetic (TC), poorly controlled diabetic (D), and nondiabetic (N) control rats were subjected to morphometric and biochemical analyses. In both tissues, capillary BM thickening was determined by electron microscopy, and FN protein level was assessed by Western blot analysis. Routine measurements of blood glucose level and glycohemoglobin level were performed throughout the study. RESULTS: The HbA1c level was significantly increased in D rats, but not in TC rats, compared with those of the N rats with a concomitant increase in capillary BM thickness and FN protein expression in retinal and renal tissues. A strong correlation was observed between retinal and glomerular capillary BM thickness (r=0.79, P=0.0001), between retinal and kidney FN protein levels (r=0.7, P=0.005), between HbA1c and FN protein levels in the retina (r=0.66, P=0.006) and kidney (r= .84, P=0.0003), and between HbA1c level and BM thickness in retinal (r=0.76, P=0.0002) and renal tissues (r=0.64, P=0.004). CONCLUSIONS: In diabetes BM thickening develops in retinal and glomerular capillaries in a correlated manner. Tight glycemic control may be beneficial in preventing the pathologic development of capillary BM thickening and FN overexpression in retinal and renal tissues, two target tissues of diabetic microangiopathy.
Authors: Alistaire D Ruggiero; Ashley Davis; Chrissy Sherrill; Brian Westwood; Gregory A Hawkins; Nicholette D Palmer; Jeff W Chou; Tony Reeves; Laura A Cox; Kylie Kavanagh Journal: Am J Physiol Regul Integr Comp Physiol Date: 2020-11-18 Impact factor: 3.619