[Ataxia-telangiectasia].
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Biomedical subjects
Publications and source records attributed to Kazuhito Fukuda.
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The spontaneously diabetic Torii (SDT) rat was recently recognized as a new animal model of non-obese type 2 diabetes. As the severe diabetic ocular complications seen in SDT rats already have been investigated, we examined another common diabetic complication, gastroenteropathy. Male SDT rats developed diabetes at 20 weeks and diarrhea at 28 weeks of age. Gastrointestinal motility was evaluated at 28 weeks by measuring the distance of small intestinal transit by oral administration of the non-absorbed marker, arabic gum. SDT rats exhibited greater intestinal transit distance than control SD rats (54.1+/-2.6% versus 43.0+/-1.2%). Insulin treatment of SDT rats begun at 20 weeks of age produced improved stool and reduced intestinal transit distance (41.4+/-0.3%). Morphologically, the SDT rats exhibited longer villi and heavier weight of intestine compared to control SD rats. These results suggest that the SDT rat may be a useful animal model for studies of diabetic gastroenteropathy.
BACKGROUND: Current success of islet transplantation has led to donor shortage and the need for marginal donor utilization to alleviate this shortage. The goal of this study was to improve the efficacy of islet transplantation using nonheartbeating donors (NHBDs). METHODS: First, we used porcine pancreata for the implementation of several strategies and applied to human pancreata. These strategies included ductal injection with trypsin inhibitor for protection of pancreatic ducts, ET-Kyoto solution for pancreas preservation, and Iodixanol for islet purification. RESULTS: These strategies significantly improved both porcine and human islet isolation efficacy. Average 399,469+/-36,411 IE human islets were obtained from NHBDs (n=13). All islet preparations met transplantation criteria and 11 out of 13 cases (85%) were transplanted into six type 1 diabetic patients for the first time in Japan. All islets started to secrete insulin and all patients showed better blood glucose control without hypoglycemic loss of consciousness. The average HbA1c levels of the six recipients significantly improved from 7.5+/-0.4% at transplant to 5.1+/-0.2% currently (P<0.0003). The average insulin amounts of the six recipients significantly reduced from 49.2+/-3.3 units at transplant to 11+/-4.4 units (P<0.0005) and five out of six patients reduced to less than half dose. The first patient is now insulin free, the first such case in Japan. CONCLUSION: This demonstrates that our current protocol makes it feasible to use NHBDs for islet transplant into type 1 diabetic patients efficiently.
Evaluation of a patient's pancreatic beta-cell function is important in both diagnosis and treatment of diabetes. We sought to determine beta-cell function with a single sampling of blood. Examination of fasting blood glucose (F-BG, mM) and C-peptide (F-CPR, nM) levels in seven post-islet-transplanted states of four patients revealed a linear relationship between F-BG and F-CPR. Assuming that normal subjects aged <40 years have 100% pancreatic beta-cell function, we developed the secretory units of islets in transplantation (SUIT) as an index of beta-cell function by the formula: 250 x F-CPR/(F-BG-3.43). The SUIT index was correlated with the stimulated C-peptide levels not only in islet-transplanted patients (R2 = 0.68, P < 0.05) but also in type 2 patients (R2 = 0.34, P < 0.001). Since the SUIT index can be calculated from data obtained at a single fasting blood sampling and predict the pancreatic beta-cell function, the formula may be a useful tool in clinical management of diabetes.
We investigated glycemic stability and insulin requirement 1 month after a single transplantation of the islets from non-heart-beating donors or a living donor. Overall blood glucose levels decreased immediately after transplantation. The M-value and mean amplitude of glycemic excursions (MAGE) decreased significantly from 53.0 (range, 8.9-91.0) to 4.2 (0.6-8.8, P<0.05) and from 8.5 mM (4.8-11.7) to 3.3 mM (2.0-4.5, P<0.05), respectively. The values after transplantation were lower than the first quartile of 102 type 2 diabetic control patients. The estimated HbA1c level decreased significantly from 7.9% (5.7-10.9) to 5.4% (4.7-5.9, P<0.05). The supplement of basal insulin decreased 43% from 0.31 units/kg/day (0.16-0.37) to 0.18 units/kg/day (0-0.22, P<0.05), while that of stimulated insulin did not decrease significantly, from 0.28 units/kg/day (0.13-0.51) to 0.21 units/kg/day (0-0.41). Thus, only one islet transplantation can be sufficient to attain metabolic stability, probably by effective supply of basal insulin secretion, sufficient to avoid life-threatening severe hypoglycemia and prevent or delay the progress of secondary complications of diabetes by decreasing the HbA1c level.
We performed the world's first successful living donor islet transplantation for unstable diabetes. A total of 408,114 islet equivalents were isolated from half a living pancreas and transplanted immediately to the recipient who was a 27-year-old female. The donor was a 56-year-old female in good health, mother of the recipient. The islets functioned immediately, and the recipient was weaned completely from insulin on the 22nd posttransplant day, and has maintained excellent glycemic control since. The donor was discharged on the 18th postoperative day with normal oral glucose tolerance test and without complications. Living donor islet transplantation could cure one insulin-dependent diabetes mellitus patients with a single donor. There are some advantages in the living donor islet transplantation: (a) living donor can alleviate the issue of donor shortage; (b) highly potent islets can be isolated from a living donor; and (c) the recipient can be treated with immunosuppressant and controlled blood glucose level tightly prior to the transplantation. These are important factors in overcoming the obstacles limiting islet transplantation. We believe that the living donor islet transplantation may become an additional option in treating insulin-dependent diabetes.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Rising demand for islet transplantation will lead to severe donor shortage in the near future, especially in countries where cadaveric organ donation is scarce. We undertook a successful transplantation of living-donor islets for unstable diabetes. The recipient was a 27-year-old woman who had had brittle, insulin-dependent diabetes mellitus for 12 years. The donor, who was a healthy 56-year-old woman and mother of the recipient, underwent a distal pancreatectomy. After isolation, 408 114 islet equivalents were transplanted immediately. The transplants functioned immediately and the recipient became insulin-independent 22 days after the operation. The donor had no complications and both women showed healthy glucose tolerance. Transplantation of living-donor islets from the distal pancreas can be sufficient to reverse brittle diabetes.