Pancreatic Islet Transplantation Using Vascularised Chambers Containing Nerve Growth Factor Ameliorates Hyperglycaemia in Diabetic Mice
A. J. HusseyMeilina WinardiJ. S. G. WilsonNatasha ForsterWayne A. MorrisonAnthony PeningtonK.R. KnightSandra J. Feeney
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Abstract:
Intraportal islet transplantation has shown initial promise for the treatment of type 1 diabetes. However, the portal vein site is associated with complications such as thrombosis and hepatic steatosis, leading to transplant failure. The aims of this study were to (1) test the feasibility of an alternative islet transplantation method that utilises a FDA-approved gelatin sponge as a novel islet carrier and (2) assess if exogenous addition of nerve growth factor (NGF) has any additional beneficial effects on graft performance in diabetic mice. Mice were rendered diabetic by a single intraperitoneal injection of streptozotocin. Five hundred syngeneic islets were seeded onto a Gelitaspon((R)) disc in the presence or absence of NGF, and placed into a silicone chamber surrounding the femoral neurovascular pedicle. Islet function was assessed by weekly monitoring of blood glucose levels and an intraperitoneal glucose tolerance test performed at the end of the study. Chambers were harvested for further histological analysis. Four of five mice transplanted with islets seeded onto Gelitaspon with NGF showed a significant reduction in blood glucose levels by 4 weeks after transplantation, and demonstrated a response similar to non-diabetic mice when tested with an intraperitoneal glucose tolerance test. Chamber tissue from this group contained islets with insulin-producing beta cells adjacent to the vascular pedicle. Islets seeded onto Gelitaspon with NGF and sited on femoral vessels using a tissue-engineering chamber offer an alternative method for islet transplantation in diabetic mice. This may have potential as a method for clinical islet transplantation.Keywords:
Intraperitoneal injection
Pancreatic Islets
Neurovascular bundle
Guinea pigs injected with streptozotocin showed temporary hyperglycemia and retardation of body growth. One month after streptozotocin injection the islets of Langerhans of these animals consisted mainly of A2-cells. Compared to the control animals the nuclei of the B- and A1-cells were increased in size. Microrespirometric analyses of the isolated islets from streptozotocin-treated animals showed that the endogenous respiratory rate was in the same range as that of islets from the controls. Addition of D-glucose to the incubation medium caused a stronger stimulation of the oxygen uptake in the control islets than in the islets from the streptozotocin-treated animals. However, when the medium was supplemented with succinate the islets from the latter animals had a higher oxygen uptake. The predominance of A2-cells in these islets supports the idea that the results are representative mainly for this cell type. The results may thus reflect a fundamental difference in the metabolism between the Band A2-cells.
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The purpose of this study was to determine species related differences in the diabetogenic response to streptozotocin (STZ) after single intraperitoneal injection. Twenty adult, male, nude rats (NR, strain Crl:NIH-Fox1 RNU ) and 8 adult, male Sprague-Dawley (SD) rats were used to induce diabetes using streptozotocin. A single, 150mg/kg STZ was injected intraperitoneally in both strains of rats. Four rats (2 from each strain) were injected buffer and served as control. Severity of the induced diabetic state was assessed by daily monitoring of body weights, clinical signs, and blood glucose levels. Four rats in the NR group died in an average of 5 days following STZ injection and 4 rats of the SD group died in an average of 2 days. In the NR group, non fasting serum glucose levels (267 ± 80 mg/dl) rose significantly (P ≤ 0.05) only in 7 (35%) rats while all SD group experienced glucose levels above 300 mg/dl (324 ± 20 mg/dl) and required insulin treatment all over the
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Aim: to create a model of stable experimental diabetes mellitus (DM) in laboratory rats using streptozotocin (STZ). Materials and methods. The dynamics of changes in glycemia and survival in 60 Wistar rats was determined. STZ at a dosage of 70 mg/kg was administered to these rats in two ways: once and fractionally (within 5 days). Results. After a single injection of the STZ, 6 out of 30 rats (20%) died, in 7 cases (23.3%) a spontaneous reversion of the diabetic status occurred and in 17 animals (56.6%) the DM remained stable throughout the observation period (8 weeks). After the fractional administration of the STZ no mortality was observed. Spontaneous reversal of DM occurred only in 2 of 30 rats (6.6% of cases). In other 28 animals hyperglycemia was stable until the end of the experiment. It is important to note that in all rats with a stable course of DM, the level of glycemia after 2 weeks after the injection of the STZ was at least 20 mmol/l. Conclusion. Fractional intraperitoneal injection of STZ has an obvious advantage compared with a single injection, providing 100% survival and stable course of DM in 93.4%. The main criterion for a stable course of experimental DM is the level of hyperglycemia not less than 20 mmol/l after 2 weeks after intraperitoneal administration of STZ.
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Objective To explore a method to develop the type 2 diabetes mellitus (T2DM) rat model. Methods Two-day-old Wistar rats (n=147) were divided into two groups: model and control groups. The modol group rats underwent intraperitoneal injection with 90 mg/kg streptozotocin (STZ). When they had ablacted they were injected with 25 mg/kg streptozotocin(STZ) again. Then these rats were fed the diets enriched with sucrose (20%) , lard(18%) and yolk powder(3%).Another group served as control group. Results Biochemical parameters and morphology proved that the methods could develop the T2DM rat model. Conclusion This method to develop T2DM rat model is high-efficient, stable and quick.
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Objective Establish a diabetic model in nude mice by intraperitoneal injection of streptozotocin and observe changes of blood glucose and pancreatic tissue.Methods Eighty nude mice were divided into four groups separately intraperitoneal injected by 0 mg/Kg,100 mg/Kg,150 mg/Kg,200 mg/Kg STZ.To evaluate the model establishment,the blood glucose of diabetic nude mice was detected with a portable glucose meter.Pancreatic pathological changes were observed under light microscope.Results In the group injected by 150 mg/Kg STZ,17 mice were found with high blood glucose after 1 week and kept high blood glucose over 16.7 mmol/L over 10 weeks.The evidences from optical microscope observation further confirmed pathological changes on pancreatic islets cells of diabetic models along with the diabetic symptoms(polydipsia,polyphagia,diuresis).Conclusion With the dose of 150 mg/Kg of STZ through once intraperitoneal injection,we can effectively induce nude mice models of diabetes mellitus,especially in a large number models and the study of tissue engineering.
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Metallothionein
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In male Wistar rats rendered diabetic by streptozotocin administration, the intraperitoneal (i.p.) injection of midazolam (2.5-5.0 and 10 mg/kg) induced a significant reduction of hyperglycemia and hyperlipidemia. The plasma immunoreactive insulin level was slightly, but significantly increased. The lethality was diminished.
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Objective To compare the success rate of taking food and fasting before induce type l diabetic rat by intraperitoneal injection Streptozotocin(50 mg/kg).Determine survival rate after two weeks.Then those model rats were applied pancreas islets transplantation.Methods 40 Wistar rats were random divided into 2 groups.The first group taking food freely before intraperitoneal inject Streptozotocin and the second group is fasting for 12 hours then intraperitoneal inject Streptozotocin.A successful model is determine by two times random blood suger level higher than 16.8 mmol/L and occurrence typical diabetes symptom for two weeks.Then determine model survival rate.Execution operation of pancreas islets transplantation.Results The first group success rate is 100%.The second group success rate is 75%.The statistics difference of success rate between two methods is less than 0.05.All model rats survived post-operation.Blood suger could reach normal level.Correlation circs need observation further.Conclusion It is a high success rate and stable method intraperitoneal injection STZ inducing diabetic rat without fasting.Model rat has good tolerance to the wound of operation.
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