Pancreas Transplantation Versus Islet Transplantation Versus Insulin Therapy in the Prevention of Nephropathy in Alloxan-Induced Diabetic Rats

doi:10.1016/S0041-1345(97)01291-8

Transplantation Proceedings

Volume 30, Issue 2, March 1998, Pages 327-329

https://doi.org/10.1016/S0041-1345(97)01291-8 Get rights and content

Section snippets

Animals and Groups

Two-hundred fifty inbred male Lewis rats, approximately 3 months old, were randomly assigned to 5 experimental groups of 50 specimens each, code-named and handled as follows: NC, nondiabetic control rats; DC, untreated diabetic control rats; I, diabetic, insulin treatment; PT, diabetic, treated with pancreas transplants from normal donor Lewis rats; and IT, diabetic, treated with pancreatic islet transplantation prepared by collagenase from normal donor Lewis rats and injected into the portal

Clinical and Laboratory

NC rats showed no evidence of clinical or metabolic abnormalities. DC rats presented a progressive loss of body weight, a significant increase in food and water intake, a significant decrease in urine output as well as increased blood and urine glucose levels, and significantly decreased plasma insulin levels. Eighteen rats (36%) in the DC group died during the follow-up as a result of the metabolic abnormalities, cachexy, or respiratory complications.

Eleven pancreas-transplanted rats (22%)

Discussion

Rats with alloxan-induced diabetes mellitus develop GBMT, ME, BCT, AE, and PRO.[11]Earlier studies have suggested that metabolic disorders, caused by functional damage to the pancreatic beta cells and leading to hyperglycemia, are the cause of diabetic nephropathy.[12]Careful glucose control then is of utmost importance in the prevention, stabilization, and reversal of chronic lesions of diabetes.

In the present study, we observed a progressive thickening of glomerular structures in all groups

First page preview

Click to open first page preview

View PDF

References (12)

S Moskalewski
Gen Comp Endocr
(1965)
RH Unger
Diabetes
(1982)
R Rash
Diabetologia
(1979)
GF Cahill et al.
N Engl J Med
(1976)
G Tchobroutsky
Diabetologia
(1978)
WV Tamborlane et al.
Diabet Care
(1982)

There are more references available in the full text version of this article.

Cited by (7)

Pancreas transplantation prevents morphologic and ultrastructural changes in pulmonary parenchyma of alloxan-induced diabetic rats
2010, Transplantation Proceedings
The aim of this study was to evaluate whether pancreas transplantation (PT) is a suitable method for controlling histopathologic changes in lungs of alloxan-induced diabetic rats.
Sixty inbred male Lewis rats were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each, which were killed after 4 and 12 weeks of follow-up. Clinical and laboratory parameters, fresh and fixed lung weights, and fixed lung volumes were recorded for all rats. Total number of alveoli, alveolar perimeter, alveolar surface area, and alveolar epithelial (AE) and endothelial capillary (EC) basal laminae thickening were randomly measured in 5 rats from each subgroup by using an image analyzer. For light microscopy, 250 alveoli were analyzed in each subgroup. For electron microscopy, 50 electron micrographs were examined for each subgroup.
The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). Fresh and fixed lung weights and fixed volumes were significantly reduced in these rats, although their proportions to body weight were increased at 12 weeks (P < .01). The total number of alveoli in diabetic rats was higher than in control rats, whereas alveolar perimeter and surface area were significantly diminished (P < .01). AE and EC basal laminae were significantly thicker in DC than in NC (P < .01). Successful PT corrected all clinical and metabolic changes in diabetic rats, with sustained normoglycemia throughout the study. Morphologic and morphometric changes observed in diabetic lungs were completely prevented in PT rats from 4 weeks after transplant.
We conclude that PT can control morphologic and ultrastructural changes in pulmonary parenchyma, suggesting a promising perspective for preventing other chronic diabetic lesions.
Pancreas Transplantation Prevents Cellular Oxidative Stress in Kidneys of Alloxan-Induced Diabetic Rats
2008, Transplantation Proceedings
Citation Excerpt :
PT impeded LPO generation and significantly increased SOD and CAT enzyme activity over the entire follow-up. These results indicated that glycemic control, with restoration of a state of permanent insulin independence and normoglycemia, seemed to be important in the genesis of ROS formation, consistent with the promising clinical benefits of PT on the evolution of all chronic diabetic lesions.19–22 Nevertheless, it is necessary to consider the control of diseases associated with diabetes, such as hypertension, hypercholesterolemia, and arteriosclerosis as being of equal importance to the genesis of hemodynamic factors when preceding ROS production in chronic diabetic nephropathy.23
Oxidative stress is one of the most important mechanisms to explain genesis of the complications in the chronic progression of diabetes. In this investigation we studied the effects of pancreas transplantation (PT) on the imbalance caused by excessive production of free oxygen radicals by antioxidant defenses of rats with serious chronic hyperglycemia induced by alloxan.
Ninety inbred male Lewis rats were randomly distributed into three groups: NC—30 nondiabetic controls; DC—30 diabetic controls without any treatment; PT—30 diabetic rats undergoing syngeneic PT from normal donor Lewis rats. Each experimental group was then split into three subgroups of 10 animals for sacrifice after 1, 3, or 6 months. Clinical and laboratory parameters from all rats as well as lipid hydroperoxide (LPO) concentrations and renal tissue enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were recorded for all rats.
Successful PT corrected clinical and laboratory alterations in diabetic rats with sustained normoglycemia throughout the study. A significant increase in LPO concentration and a marked reduction in SOD and CAT enzyme activity were observed in DC rats; there was no significant variation in renal tissue GSH-Px in this group. However, alterations in DC rats were completely restored from 1st month after PT; all evaluated enzyme levels did not significantly differ (P < .01) from those in NC controls.
Successful PT controlled cellular oxidative stress in diabetic kidneys, which may prevent chronic lesions.
Islet Transplants for Diabetes: The Edmonton Protocol
2007, Cellular Transplantation
Islet transplants for diabetes: The Edmonton Protocol
2006, Cellular Transplantation: From Laboratory to Clinic
Long-term effects of insulin therapy, islet transplantation, and pancreas transplantation in the prevention of glomerular changes in kidneys of alloxan-induced diabetic rats
2005, Transplantation Proceedings
Groups of inbred alloxan-induced diabetic rats were treated with insulin (I), islets (IT), or pancreas transplantation (PT). Nondiabetic (N) and untreated diabetic (D) control groups were concurrently included. Each group was divided into five subgroups of 10 rats and killed after follow-up of 1, 3, 6, 9, and 12 months. Clinical and laboratory parameters were recorded, and kidney ultrastructural and morphometric analyses performed in each 12-month subgroup, namely glomerular basement membrane (GM) thickening, podocyte number, and number/extension of slit diaphragms (S). Rats from the I group showed poor metabolic control of diabetes compared with N group control rats. However, successfully transplanted rats (IT and PT) had complete restoration to normal levels for all metabolic parameters. GM thickening was significantly higher in diabetic compared with control rats. In contrast, the numbers of podocytes and slits as well as slit extensions were significantly decreased. Insulin therapy did not prevent any alterations upon comparison of diabetic vs control rats. Despite good metabolic control in IT rats, the degree of kidney lesion control never compared with that achieved in PT rats. In this group all glomerular changes were similar to the age-dependent lesions observed in control rats. We conclude that either IT or PT may be a good option for diabetes treatment, although pancreas transplantation seems to be the most effective treatment to control chronic complications.
Successful islet transplantation does not prevent the development of neuropathy in alloxan-induced diabetic rats
2002, Transplantation Proceedings

View all citing articles on Scopus

¹: Research supported by FAPESP.

View full text

Original ArticlesPancreas Transplantation Versus Islet Transplantation Versus Insulin Therapy in the Prevention of Nephropathy in Alloxan-Induced Diabetic Rats 1

Section snippets

Animals and Groups

Clinical and Laboratory

Discussion

First page preview

Gen Comp Endocr

Diabetes

Diabetologia

N Engl J Med

Diabetologia

Diabet Care

Original Articles
Pancreas Transplantation Versus Islet Transplantation Versus Insulin Therapy in the Prevention of Nephropathy in Alloxan-Induced Diabetic Rats ¹