The organization of the endocrine pancreas: a hypothetical unifying view of the phylogenetic differences.
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Amphibians↗
Biomedical subjects
S Bonner-Weir
Publications and source records attributed to S Bonner-Weir.
Effects of glutamine-enriched parenteral nutrition on the exocrine pancreas.
Total parenteral nutrition (TPN) is associated with intestinal and pancreatic atrophy and pancreatic exocrine insufficiency. Recent investigations have demonstrated that the addition of glutamine to intravenous feedings attenuates TPN-associated intestinal atrophy. However, the effect of glutamine-supplemented intravenous feedings on the pancreas of intact animals is unknown. This study compared the effects of an intravenous infusion of a 2% glutamine-enriched diet (GLN) with an isonitrogenous, isocaloric diet without glutamine (CONT) on the composition and structure of the exocrine pancreas in laboratory rats with and without a 60% small bowel resection. In nonresected, TPN-fed animals, pancreatic weight was significantly increased in the GLN group when compared to CONT (645 +/- 33 g vs 554 +/- 20 g, p less than 0.05). Nonresected GLN animals also had increased pancreatic DNA (3.82 +/- 0.19 mg vs 2.91 +/- 0.49 mg, p less than 0.005) and protein contents (93.0 +/- 5.9 mg vs 76.6 +/- 7.0 mg, p = 0.08) compared to control. Similar significant increases in pancreatic weight, DNA, and protein were observed in intestinally resected animals fed the glutamine diet. When data from CONT and GLN animals were pooled and analyzed together, glutamine significantly increased total pancreatic trypsinogen and lipase contents (p less than 0.05). The increase in trypsinogen in resected GLN animals was significantly greater than in CONT animals (283 +/- 22 vs 139 +/- 23, p less than 0.005). Biochemical and morphometric observations demonstrated that the trophic effects of glutamine on the exocrine pancreas were manifest by acinar hyperplasia and not hypertrophy. Glutamine appears to be an important nutrient for pancreatic exocrine tissue during TPN.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.
Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.
Animals↗
A method for estimating number and mass of islets transplanted within a membrane device.
Immunobarrier devices may prevent the immune destruction of pancreatic islets transplanted into diabetic recipients, but there are concerns about the survival of islets within such devices. In this manuscript we described a method for estimating islet mass and number within a membrane device. Five hundred syngeneic mouse islets were placed in a membrane device, which was then transplanted into the epididymal space of streptozotocin diabetic mouse. After 14 days the device was removed from the recipient, fixed, and embedded in paraffin. Sections were made and then stained with hematoxylin. From a total of 58 sections, 12 sample sections were selected for analysis by computerized planimetry to determine area of the device chamber and the islet area for each of these sections. By making certain assumptions, it was possible to estimate the total volume of the device chamber, the number of islets contained within the chamber, and the mass of islet tissue. Two weeks after implantation of the chamber, to which approximately 500 microencapsulated islets were loaded, the blood glucose level of the recipient fell to 73 mg/dL. The volume of the device chamber, the total volume of islets in the device, and the total islet number within the device were 1.78 microL, 0.57 microL, and 277 islets, respectively. The detailed methodology, assumptions, and calculations for this approach are described in this manuscript. This new method makes it possible to determine islet mass within a membrane device by analyzing a relatively small number of selected sections. This approach should make it possible to carry out comprehensive studies on the fate of transplanted islets contained in such immunobarrier membrane devices.
Animals↗
Number and volume of islets transplanted in immunobarrier devices.
Immunobarrier devices may prevent immune destruction of transplanted islets, but there are concerns about survival within such devices. Islets were transplanted in diffusion chambers that employed two laminated polytetrafluoroethylene membranes held together with titanium rings. Five hundred syngeneic mouse islets placed in devices were transplanted into the epididymal fat pads of streptozotocin (STZ) diabetic mice (B6AF1). After 2 wk the devices were removed. Sections were made parallel to the membrane surface. Eight to 13 systematically selected sections of each device were analyzed by planimetry to determine the area of the device space and of the islets within that space. From these data we estimated total volume of the device, volume of islets, and number of islets in a device. The data were segregated into two groups: group I (blood glucose less than 100 mg/dL 2 wk after implantation), and group II (over 150 mg/dL). The volume (mean +/- SE) of devices implanted for 2 wk was 2.1 +/- 0.4 microL in group I and 2.2 +/- 0.2 microL in group II. The islet volume and number within devices were 0.30 +/- 0.06 and 0.17 +/- 0.01 microL, or 340 +/- 50 and 230 +/- 20 islets in group I and group II, respectively. The volume of fibrous tissue in devices was about 0.50 microL. About 10% of the islet tissue had central necrosis. The beta cell volume in a membrane device needed for cure is comparable to that required with islets under the kidney capsule (0.25-0.80 microL). The mass of islets contained within membrane devices needed to cure diabetes is equivalent to that of a graft in an optimal transplant site such as under the kidney capsule.
Animals↗
Differentiation and expansion of beta cell mass in porcine neonatal pancreatic cell clusters transplanted into nude mice.
Neonatal porcine pancreas has considerable capacity for growth and differentiation, making it an attractive potential source of islet tissue for xenotransplantation. Pancreases from 1-3-day-old newborn pigs were digested with collagenase and cultured for 8 days. The resulting cellular aggregates are called porcine neonatal pancreatic cell clusters (NPCCs). The mean yield of NPCCs from a newborn pig was 28,200 +/- 1700 islet equivalents. Cytokeratin 7 (CK7) was used as a marker for the immunostaining of pancreatic duct cells. In neonatal pancreas, 18% of the insulin-positive cells co-stained for CK7, thus being protodifferentiated. NPCCs also contained protodifferentiated cells; insulin/PP and insulin/somatostatin co-stained cells were more common than insulin/glucagon cells. Between 1 and 8 days of culture, the DNA content of the NPCCs fell to 16% and the insulin content to 33% of the starting value, mainly due to the preferential loss of exocrine cells. Transplantation of 2000 or 4000 NPCCs into diabetic nude mice typically normalized glucose values in 10-20 weeks. Mice with successful grafts had lower fasting blood glucose levels than normal mice and accelerated glucose clearance after an i.p. glucose load. The starting NPCCs consisted of 17% insulin-staining cells, but the grafts of mice with reversed diabetes consisted of 94% beta cells, with some co-stained for CK7, indicating that the grafts still contained immature cells. The mass of insulin-producing cells rose from 0.22 +/- 0.08 mg 1 week after transplantation to 4.34 +/- 0.27 mg in mice sacrificed at 27-35 weeks. In summary, NPCCs contain mostly islet precursor cells, which when transplanted into nude mice undergo striking differentiation and beta cell expansion.
Animals↗