Basal Lamina Layering in Diabetes Mellitus: Evidence for Accelerated Rate of Cell Death and Cell Regeneration

Abstract

Excessive deposition of basal lamina in capillaries and othei structures of individuals with diabetes mellitus is characterized by formation of multiple layers of basal lamina and accumulation of cell debris between the layers. In capillaries with multiple BL layers, between pericytes and endothelial cells, only a single layer is generally present These and other features suggest that basal lamina formation is a quantified event and that excessive accumulation could be the result of (1) cell death and cell replacement, (2) discrete turning on and off of basal lamina production or (3) defective resorption of old basal lamina layers. Evidence indicating that the major component in the pathogenesis of basal lamina accumulation is cell death and cell regeneration is presented. Whether interrupted production or impaired resorption also contribute to this process is unknown. The common presence of BL layering in patients with diabetes mellitus indicates that diabetics' cells are different from nondiabetics', the difference manifesting itself by increased rate of cell death. The focal nature of this process suggests further that injurious events in the cells' environment contribute to the pathogenesis of this lesion.Whatever the cause, the BL characteristics discussed, like rings on cross-sections of tree trunks, give some indication of the number of cell generations which have occurred at that particular site. DIABETES 23:94-104, February, 1974.In patients with diabetes mellitus several related lesions are caused by excessive accumulation of basal lamina (BL).* The lesions are encountered not only in capillaries, where they give rise to diabetic microangiopathy and glomerulosclerosis, but also in many other sites where BL is normally present. Accumula-*Basal lamina (BL) is used synonymously with basement membrane and basement lamina.

Acute Renal Failure after Analgesic Drugs Including Paracetamol (Acetaminophen)

“…This ob servation may therefore be an indication of a pathologi cal state of endothelial regeneration, where the normal turnover is exaggerated. Such an explanation has been proposed by Vracko [24] for the small vessel disease in diabetes mellitus. Certainly, it can only be detected with the electron microscope and even then it may be difficult to perceive if not especially sought.…”

Structural manifestations of diabetic cardiomyopathy in the rat and its reversal by insulin treatment

“…An alternative hypothesis for basal lamina thickening, particularly in the renal glomerulus, is based upon the observation that capillaries in diabetes are more permeable to plasma proteins (Parving, 1976), which may extravasate and become embedded in the less-permeable basement membrane. It has also been suggested that reduplication and thickening may represent remnants of repeated capillary degeneration and repair (Vracko, 1974;Williamson and Kilo, 1977), although if this were the case it would be difficult to explain the absence of basal lamina abnormalities in tissue from the insulintreated animals. At the other end of the spectrum, some investigators believe that these changes precede any defect in plasma glucose regulation or metabolism (Siperstein et al, 1966).…”

Observation on the Basal Lamina of Duodenal Epithelial Cells during Metamorphosis of Xenopus laevis

“…However, in the presence of a pathologic condition, the basal lamina undergoes morphologic changes. In patients with diabetes mellitus, the basal lamina of capillaries exhibits a multi-layered structure (Vracko, 1974). Multiple layers and branching of the basal lamina have also been described as a feature of mammary dysplasia (Ahmed, 1974;Ozzello, 1970Ozzello, , 1971Ozzello, , 1984Hassan et al, 1979).…”