Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Islets of Langerhans surrounded by a semipermeable membrane to prevent an immune response by the host immunosystem is a potential way of treating type I diabetes mellitus. In this study, poly(vinyl alcohol) (PVA) tubular membranes with added polyethylene glycol to create pores in the skin layer were prepared to improve their diffusion property. In a static incubation study, islets cultured in the PVA tubular membranes still demonstrated their function of secreting insulin after 30 days. When the tubular PVA bioartificial pancreas was perifused in a small chamber with RPMI-1640 medium containing glucose at concentrations of 5.6-16.6 mmol/L, insulin release began to increase without delay. Therefore, such a membrane is an alternative potential material for a bioartificial pancreas. In addition, a mathematical mass transfer model of insulin release was developed and compared with the perifusion data. It was shown that satisfactory kinetics could be achieved with a PVA membrane. However, the model showed that the insulin output of islets cultured in the PVA tubular membrane must be increased to improve the performance significantly. These findings suggest that a bioartificial pancreas using a PVA membrane is a promising material, but the technique for seeding islets in the chamber requires further modification.
 ...
PMID:Use of a diffusion model for assessing the performance of poly(vinyl alcohol) bioartificial pancreases. 957 69

Pancreatic islets surrounded by a semipermeable membrane to prevent an immune response by the host immunosystem is a potential way of treating type I diabetes mellitus. Our previous in vitro studies have demonstrated that poly(vinyl alcohol) (PVA) membranes satisfy the basic requirements for a bioartificial pancreas. This study was designed to evaluate the performance of PVA tubular membrane chambers containing islets in vivo. When the m-2 type of PVA chamber was implanted into streptozotocin-induced diabetic rats, nonfasting blood glucose levels dropped from 500 +/- 35 mg/dl to the lowest value 210 +/- 22 mg/dl. Furthermore, the performance of the bioartificial pancreas can be enhanced by the increased numbers of implanted chambers. If three m(-2) chambers were implanted, nonfasting blood glucose levels in the diabetic rats decreased to 130-160 mg/dl and such a low blood glucose value was maintained for 1 month. This indicates that implanting three m-2 chambers in the diabetic rats could provide improved permeability of insulin to normalize blood glucose levels and improved survival of islets from the immune system of the recipient. For improving the design of the bioartificial pancreas, a mathematical model was developed to account for the changes in blood glucose levels of the diabetic rats. We demonstrated such a mathematical analysis was helpful to understand the characteristics of islet inside an artificial environment.
 ...
PMID:Assessment and modeling of poly(vinyl alcohol) bioartificial pancreas in vivo. 1209 94

Altered cardiac metabolism and function (diabetic cardiomyopathy) has been observed in diabetes. We hypothesize that cardiac efficiency, the ratio of cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption (MVo(2)), is reduced in diabetic hearts. Experiments used ex vivo working hearts from control db/+, db/db (type 2 diabetes), and db/+ mice given streptozotocin (STZ; type 1 diabetes). PVA and ventricular function were assessed with a 1.4-F pressure-volume catheter at low (0.3 mmol/l) and high (1.4 mmol/l) fatty acid concentrations with simultaneous measurements of MVo(2). Substrate oxidation and mitochondrial respiration were measured in separate experiments. Diabetic hearts showed decreased cardiac efficiency, revealed as an 86 and 57% increase in unloaded MVo(2) in db/db and STZ-administered hearts, respectively. The slope of the PVA-MVo(2) regression line was increased for db/db hearts after elevation of fatty acids, suggesting that contractile inefficiency could also contribute to the overall reduction in cardiac efficiency. The end-diastolic and end-systolic pressure-volume relationships in db/db hearts were shifted to the left with elevated end-diastolic pressure, suggesting left ventricular remodeling and/or myocardial stiffness. Thus, by means of pressure-volume technology, we have for the first time documented decreased cardiac efficiency in diabetic hearts caused by oxygen waste for noncontractile purposes.
 ...
PMID:Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. 1644 82

Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices were then implanted into diabetic rats where reduced insulin requirement was noted suggesting insulin secretory activity of islets contained in the device. Indeed, immunofluorescence confirmed the presence of insulin- and glucagon-producing cells into the explanted devices. These data show that PVA/PEG semi-permeable membrane can obtain devices that restore, at least in part, insulin secretion.
 ...
PMID:Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: in vitro and in vivo studies. 2004 27

Pancreatic differentiation of stem cells will aid treatment of patients with type I diabetes mellitus (T1DM). Synthetic biopolymers utilization provided extracellular matrix (ECM) and desired attributes in vitro to enhance conditions for stem cells proliferation, attachment and differentiation. A mixture of polycaprolactone and polyvinyl alcohol (PCL/PVA)-based scaffold, could establish an in vitro three-dimensional (3D) culture model. The objective of this study was investigation of the human induced pluripotent stem cells (hiPSCs) differentiation capacity to insulin-producing cells (IPCs) in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels by quantitative PCR and immunofluorescence assay, respectively. The functionality of differentiated IPCs was assessed by C-peptide and insulin release in response to glucose stimulation test. Real-Time PCR results showed that iPSCs-IPCs expressed pancreas-specific transcription factors (Insulin, Pdx1, Glucagon, Glut2 and Ngn3). The expressions of these transcription factors in PCL/PVA scaffold were higher than 2D groups. In addition to IPCs specific markers were detected by immunochemistry. These cells in both groups secreted insulin and C-peptide in a glucose challenge test by ELISA showing in vitro maturation. The results of current study demonstrated that enhanced differentiation of IPCs from hiPSCs could be result of PCL/PVA nanofibrous scaffolds. In conclusion, this research could provide a new approach to beta-like cells replacement therapies and pancreatic tissue engineering for T1DM in the future.
 ...
PMID:PCL/PVA nanofibrous scaffold improve insulin-producing cells generation from human induced pluripotent stem cells. 2986 65