Biomedical subjects
Publications and source records attributed to J Duhault.
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The ultrastructure of the nervous elements in Langerhans islets of Psammomys obesus has been studied. A great variety of neural structures present in the islets has been described: neuroganglion-, enterochromaffin- and satellite Schwann cells (neuro-insular complexes type I) and cholinergic, adrenergic and peptidergic nerve fibers (neuro-insular complexes type II) in direct contact with the endocrine cells. In the pericapillary space typical neuro-vasal endings of neurosecretory type have been described. The islets of Langerhans and some of the endocrine cells have a total or partial glial sheath. These findings support the thesis of the paraneuronal nature of the endocrine cells of the Langerhans islets.
A morphological analysis of the endocrine pancreas in the normoglycemic sand rat (Psammomys obesus) has been carried out and the immunoreactivity for insulin, glucagon, somatostatin and pancreatic polypeptide (PP) studied. The islets of both parts of the pancreas (pancreatic head and tail) investigated were of the 'mantle' type: centrally located B-cells and A-, D- and PP-cells at the periphery. In the 'glucagon islets' (tail of pancreas) predominated the A-cells, while the PP-cells were more abundant in the "PP-islets' (head of the pancreas).
The effect of 1-(m-trifluoromethylphenyl)-2-(beta-benzoyloxyethyl)-amino- propane hydrochloride (780 SE) on serum lipids, blood glucose and liver weight was studied in 4 experimental models, and compared with that of clofibrate and tiadenol. When rats were given a daily oral dose of 25 mg/kg or 50 mg/kg of 780 SE for 5 days a marked reduction of serum triglycerides and liver weight was observed. The decreases were more pronounced than those in rats treated with 50 mg/kg or 100 mg/kg of clofibrate or tiadenol. On the other hand, a reduction of serum cholesterol was only observed in the groups given clofibrate and tiadenol. These differences could be explained on the basis of the mechanism of action of the different drugs. Only 780 SE induced a decrease in blood sugar level, a reduction of plasma insulin concentration and restored the insulin sensitivity to a normal value in obese animals. There was a significant decrease in liver weight of 780 SE treated rats, whereas clofibrate and tiadenol cause hepatomegaly.
Reactive oxygen species (ROS) play an important role in signaling pathways stimulated by growth factors in vascular cells. We investigated whether vascular endothelial growth factor (VEGF), which is upregulated in diabetic retinopathy and atherosclerosis, is able to enhance production of ROS, and if so, whether ROS modulate endothelial permeability. ROS levels in bovine retinal microvascular endothelial cells (BMEC) were measured by the oxidation of 2', 7'-dichlorodihydrofluorescein (DCHF), and permeability was examined by monitoring the passage of albumin through BMEC monolayers. VEGF stimulated oxidation of DCHF in BMEC, an effect which was inhibited by superoxide dismutase (SOD) and the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), but not by D-NAME. Urate, a scavenger of peroxynitrite, attenuated the VEGF-induced oxidation of DCHF. VEGF elicited a significant increase in the macromolecule permeability of BMEC monolayers within 30 min. SOD did not modify the basal or the VEGF-stimulated hyperpermeability, but the combination of SOD and VEGF induced a transient reduction in permeability after 10 min. L-NAME, but not D-NAME, enhanced VEGF-induced hyperpermeability without affecting basal values. Urate did not modify the VEGF-induced changes in permeability. In conclusion, VEGF stimulates oxidation of DCHF, which most likely represents peroxynitrite formation, and induces an increase in permeability of BMEC monolayers. Activation of NO synthase seems to counteract this stimulatory effect of VEGF on endothelial permeability.
The aim of the present study is based on the comparison of intravenous tolerance testing before and after segmental pancreas autotransplantation in the dog. The results show that such testing must take in account the "glucose diffusion space", using the same glucose load in order to avoid the bias related to the post-operative loss of body weight.
Segmentary heterotopic autotransplantation of the body and tail of the pancreas, with visceral exocrine drivation and splenosplenic arterio-venous fistulation, was performed in 12 Beagle dogs. An in vivo glucose tolerance test was conducted before the transplantation and 21 days after the operation. There was a significant decrease in the k coefficient (2.884 +/- 0.234 before and 1.878 +/- 0.128 after transplantation) due to reduced peripheral glucose uptake after transplantation (p < 0.001). Overall glucose-stimulated insulin production was decreased after < 0.001). Two populations were identified retrospectively: in 7 dogs insulin response was satisfactory after transplantation (insulin production > or = 50% pretransplantation level) and in 5 the response was below 50%. Glucose tolerance was tested in vitro in the isolated perfused pancreas transplant in 9 dogs, 30 days after the transplantation. Secretory response was assessed according to the early peak of insulin secretion after glucose stimulation. The patterns of insulin secretion were not different before glucose stimulation but became statistically different after stimulation (p < 0.001). In 5 dogs, the response to in vitro glucose stimulation showed an early peak in insulin secretion and in 4 dogs the insulin response came late with no early peak. On histological examination normal (or subnormal) pancreas grafts and grafts in which extensive sclerosis impaired function could be distinguished. There was a significant correlation between the quality of function and the histology, suggesting that containing post-operative sclerosis to a minimum is an important factor in human transplantations.
This review presents the major animal models usually used for the study of the pathological processes related to insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) and to the main diabetic complications. These models can be observed spontaneously or can be obtained by selective cross-breeding or toxic exposure (chemical or viral), as well as genetically induced. They reproduce some aspects of the human pathology without combining them all in a single model. Consequently, a pertinent pharmacological approach may compare the results obtained with several models. The examination of the recent results obtained with transgenesis does not allow these animal models to replace more classical ones but they may constitute a future challenge for gene therapy despite the multifactorial aspect of diabetic disease.
Diabetes produces dramatic changes in retinal microvasculature, triggering endothelial cell proliferation and microaneurysms. Capillaries become weakened, releasing blood into vitreal and retinal spaces. Photoreceptors become occluded and separated from the choriocapillaris, resulting in visual acuity decline, detachment and cell death. Several models have been developed that have proved useful for the study of this disease, resulting in a better understanding of the processes involved. Streptozotocin treatment affects the pancreatic beta cells, rapidly reducing them until insulin is no longer synthesized in sufficient amounts. The galactosemic model shifts metabolism away from glucose, increasing aldose reductase and retinal polyol metabolism. Finally, two weeks of cycled oxygen from high to low tension every 24 hours, followed by return to room air, triggers microangiogenesis in developing retinas. Use of these models, separately or in combination, as well as electroretinographic analysis, has begun to reveal the events taking place as diabetic retinopathy progresses. Endothelial cells become separated from pericytes as basement membranes thicken, and vascular endothelial growth factor increases, triggering their proliferation. Finally, early changes occurring within photoreceptors can now be studied.