ABSTRACT

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.

Oligodendrocytes in the ganglion cell layer, the myelinating cells in the chicken retina, were investigated morphologically and quantitatively. Oligodendroblasts divided in the inner retinal layer around the 14th day of incubation and differentiated into oligodendrocytes. The oligodendrocytes started sheathing an axon in the nerve fiber layer at the 14th day of incubation. The number of myelin lamellae increased rapidly during the first week after chicks had hatched. An immunological reaction of anti-myelin basic protein was observed on the myelin sheaths in the nerve fiber layer and on the oligodendrocytes in the ganglion cell layer. These results suggest that the oligodendrocytes form the myelinated nerve fiber layer of the chicken and that they act independently of the Müller cells during myelination.

The fluorescent granular perithelium (FGP) of rats and humans under experimental and pathological conditions was examined with the electron microscope. The FGP incorporated high molecular-weight protein (ferritin) and carbon particles administered intraventricularly. In a case of spontaneous cerebral hemorrhage, the FGP was found to contain lipoidal products and minute fragmented cell debris. The FGP in a patient with lipidosis contained pale inclusion bodies. In aged individuals, the inclusion bodies formed irregular larger aggregates.

The tridimensional appearance and distribution of FGP (fluorescent granular perithelial) cells was studied by means of light and scanning electron microscopy. In young rats they first appeared as hexagonal cells in that were closely associated; later they transformed into slender forms and were loosely arranged. Scanning electron microscope observation gave a general view of FGP cells, their globular vacuolated inclusions, and their hypertrophied protrusion into the luminal surface of blood vessels. The nodular protrusions may be related to the limitation of blood flow in small cerebral blood vessels.