Young Lewis rats will be subjected to alloxan 42 mg/kg iv injection and diabetic state will be determined by 2 consecutive blood sugar determinations at one week intervals. Animals will be divided into Control (diabetic rats with no transplants) and Experimental Group. The Experimental Group will be divided into 6 subgroups: at their alloxan diabetic month 6, 9, 12, 15, 18, 21. Brown Norway (BN) pancreaticoduodenum (PD) will exclusively be transplanted and an immediate treatment with Cyclosporin-A, 15 mg/kg per day for 10 days, will be instituted. At the time of PD transplantation, vital organs of the recipients (kidney, liver, peripheral nerve, muscle, testes and epididymis) will be subjected to biopsy (light and electron microscopy). In order to match our pervious work, animals will be sacrificed at scheduled periods: Exp. Group I 3 rats will be sacrificed each month for 18 months; II - 3 rats will be sacrificed each month for 15 months; III - 3 rats will be sacrificed each month for 12 months; IV - 3 rats will be sacrificed each month for 6 months; V - 3 rats will be sacrificed for 6 months; VI - 3 rats will be sacrificed each month for 3 months. A complete autopsy of all vital organs including (1) kidney, (2) eyes, (3) host pancreas, (4) graft pancreas, (5) sciatic nerve, (6) brain-spinal cord, (7) liver, (8) heart-lung, (9) great vessels, (10) intestine, (11) adrenal, (12) testicles, (13) epididymis, (13) muscle. A periodical pre- and post-transplantation metabolic study will be conducted. A special emphasis on Cyclosporin-A toxicity on vital organs will be carefully observed throughout the experimental periods, especially during the full life span of diabetic rats.
| Mitch, W E; Bailey, J L; Wang, X et al. (1999) Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. Am J Physiol 276:C1132-8 |
