Islets from brain-dead donors (BDDs) are being used in the treatment of Type 1 diabetes. However, both donor numbers and islet survival are limited. We explored the clinical potential for islets from non-heart-beating donors (NHBDs), who have lower circulating cytokines, by comparing islets from 10 NHBDs against 12 identically-isolated islets ...

Success of transplantation of pancreatic islets which is a promising way for restoring efficient insulin regulation in type 1 diabetes depends on lifelong use of immunosuppressive drugs. To eliminate the use of systemic immunosuppressive drugs for islet transplantation, we examined the potential use of a local immunosuppressive factor, indoleamine 2,3-dioxygenase ...

The relationship between type 2 diabetes mellitus and pancreatic cancer (PC) is not clear. It has been reported that the increased release of islet amyloid polypeptides (IAPPs) is responsible for the impaired glucose tolerance in PC patients. However, no information exists on the patterns of IAPP expression in PC tissue ...

Human islet-derived precursor cells (hIPCs), mesenchymal cells derived in vitro from adult pancreas, proliferate freely and do not express insulin but can be differentiated to epithelial cells that express insulin. hIPCs have been studied with the goal of obtaining large quantities of insulin-producing cells suitable for transplantation into patients suffering ...

Pancreatic islet cell death is the cause of deficient insulin production in diabetes mellitus. Approaches towards prevention of cell death are of prophylactic importance in control and management of hyperglycemia. Generation of oxidative stress is implicated in streptozotocin, a beta cell specific toxin-induced islet cell death. In this context, antioxidants ...

It has been proposed that de novo synthesis of long-chain acyl-CoA (LC-CoA) is a signal for glucose-stimulated insulin secretion (GSIS). Key enzymes involved in synthesis of fatty acids from glucose include ATP-citrate lyase (CL) and fatty acid synthase (FAS). An inhibitor of CL, hydroxycitrate (HC), has been reported to inhibit ...

Deposition of islet amyloid polypeptide (IAPP) as amyloid in the pancreatic islet occurs in approximately 90% of individuals with Type 2 diabetes and is associated with decreased islet beta-cell mass and function. Human IAPP (hIAPP), but not rodent IAPP, is amyloidogenic and toxic to islet beta-cells. In addition to IAPP, ...

We previously demonstrated the development of beta-cells in the native pancreas after syngeneic pancreas transplantation (PTx) in a model of type 2 diabetes, namely the Spontaneously Diabetic Torii (SDT; RT1 a) rat. In this study, we evaluated the effect of fully allogeneic PTx (allo-PTx) under immunosuppression on the native pancreases ...

Previous studies have shown that Prostaglandin E(2) (PGE(2)) inhibits glucose-stimulated insulin secretion. However, the role of cyclooxygenase (COX)-1 vs. COX-2 derived PGE(2) production in glucose-stimulated insulin secretion remains poorly understood. Here we investigated the expression of COX-1 and COX-2 in pancreatic islets and the effect of selective inhibition of COX-1 ...

We investigated the effect of sub-chronic soybean oil (SO) treatment on the insulin secretion and fatty acid composition of islets of Langerhans obtained from Goto-Kakizaki (GK), a model of type 2 diabetes, and normal Wistar rats. We observed that soybean-treated Wistar rats present insulin resistance and defective islet insulin secretion ...

An animal model of post-transplant diabetes was induced in rats by treating them daily with 0.1 mg/kg body weight of tacrolimus (FK506) in two i.p. injections. Rats developed hyperglycaemia and glucose intolerance after 9 days of treatment. Pancreatic islets, isolated from treated rats on different days, showed a decreased capacity ...

Neuropeptide Y (NPY), whose role in appetite regulation is well known, is also expressed in pancreatic islets. Although previous studies indicated that application of NPY to pancreatic islets inhibits insulin secretion, its physiological role in the regulation of insulin secretion is not fully understood. We hypothesized that NPY in islets ...

Restricted Item. Print thesis available in the University of Auckland Library or available through Inter-Library Loan. Human amylin (HA), a 37 amino acid peptide, was purified as the major constituent of the amyloid plaques deposited within the extracellular spaces of the pancreatic islets of Langerhans of Type 2 Diabetes Mellitus ...

OBJECTIVE: The pathogenesis of type 1 diabetes involves autoimmune lymphocytic destruction of insulin-producing beta-cells and metabolic dysregulation. An early biomarker of pancreatic islet damage is islet microvascular dysfunction, and alterations in vascular volume, flow, and permeability have been reported in numerous models of type 1 diabetes. Consequently, the ability to ...

The spontaneously diabetic Goto-Kakizaki (GK) rat is frequently used as a model for human type 2 diabetes. Selective loss of glucose-sensitive insulin secretion is an early pathogenetic event in human type 2 diabetes, and such a defect also typifies islets from the GK rat. We investigated whether expression of specific ...

The promising results obtained using the "Edmonton protocol" for human islet transplantation has resulted in increased interest and growth of various clinical and basic science programs worldwide. Despite these encouraging results two major drawbacks remain: first, the immunosuppressive regimen necessary to prevent the rejection of this allotransplant dramatically affects the ...

Impairment of insulin secretion from the beta-cells of the pancreatic islets of Langerhans is central to the development of type 2 diabetes mellitus and has therefore been the subject of much investigation. Great advances have been made in this area, but the mechanisms underlying the pulsatility of insulin secretion remain ...

Emerging evidence over the past decade indicates a central role for transcription factors in the embryonic development of pancreatic islets and the consequent maintenance of normal glucose homeostasis. Pancreatic and duodenal homeobox 1 (Pdx1) is the best studied and perhaps most important of these factors. Whereas deletion or inactivating mutations ...

In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance-trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic beta-cells and to monitor, non-invasively in real-time, hepatic delivery and ...

AIMS/HYPOTHESIS: Hyperglycaemia can impair beta cell function after islet transplantation. Appropriate glucose-induced insulin secretion is dependent on a unique expression pattern of genes. Here we examined the effects of diabetes on gene expression in transplanted islets. MATERIALS AND METHODS: Streptozotocin-induced diabetic or control non-diabetic Lewis rats were transplanted under the ...

BACKGROUND: Whether islet transplantation should be aimed at restoring insulin independence or providing adequate metabolic control is still debated. The GRAGIL2 trial was designed as a phase 1-2 study where primary outcome was the rate of insulin independence, and secondary outcome was the success rate defined by a composite score ...

Bank voles (Clethrionomys glareolus) kept in captivity develop diabetes mellitus to a significant extent. Also in wild bank voles, elevated blood glucose has been observed. A newly isolated picornavirus named Ljungan virus (LV) has been found in the pancreas of these bank voles. Moreover, LV infection in combination with environmental ...

Amyloid deposits derived from the amylin peptide accumulate within pancreatic islet beta-cells in most cases of type-2 diabetes mellitus (T2Dm). Human amylin 'oligomers' are toxic to these cells. Using two different experimental techniques, we found that H(2)O(2) was generated during the aggregation of human amylin into amyloid fibrils. This process ...

INTRODUCTION: Rejection and hypoxia are the main factors that limit islet engraftment in the recipient liver in the immediate posttransplant period. Recently authors have reported a negative relationship of graft function and islet size, concluding that small islets are superior to large islets. Islets can be dissociated into single cells ...

Ghrelin has a correlation with insulin secretion, beta-cell development, and diabetes in crucial development period. The aim of this study was to compare the changes in plasma ghrelin, insulin, and glucose concentrations, and variation of ghrelin expression in the pancreas in response to intrauterine malnutrition in newborn rats. Pregnant rats ...

This review focuses primarily on islet structural and functional changes related to an activated islet renin- angiotensin system (RAS), islet oxidative-redox imbalance, the concurrence of islet fibrosis (pericapillary, intra- and peri-islet), and islet amyloid deposition (pericapillary, intra- and peri-islet). The islet-acinar-portal vascular pathway and the emerging important anatomical and functional ...

Allogeneic and autoimmune islet destruction limits the success of islet transplantation in autoimmune diabetic patients. This study was designed to investigate whether ex vivo gene transfer of viral interleukin-10 (vIL-10) protects BioBreeding (BB) rat islets from autoimmune destruction after transplantation into diabetic BB recipients. Islets were transduced with adenoviral constructs ...

The feasibility of myoglobin (Mb)-facilitated oxygen transport in improving porcine islet survival under hypoxia was investigated. Discrete groups of islets were transfected with replication-defective adenoviral vector Ad5 respiratory syncitial virus (RSV) to induce expression of Mb or green fluorescent protein (GFP). Native islets served as the controls. In vitro studies ...

The contribution of Na(+)/H(+) exchange (achieved by NHE proteins) to the regulation of beta-cell cytosolic pH(c), and the role of pH(c) changes in glucose-induced insulin secretion are disputed and were examined here. Using real-time PCR, we identified plasmalemmal NHE1 and intracellular NHE7 as the two most abundant NHE isoforms in ...

Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, but only a small fraction of implanted islets become engrafted. The underlying mechanisms remain elusive. To probe the mechanism of islet revascularization, we determined the effect of angiopoietin-1 (Ang-1), a proangiogenic and antiapoptotic factor, on the survival, ...

OBJECTIVES: Xenotransplantation of pig islets is a potential solution to the shortage of human islets, but our knowledge of how these islets secrete insulin in response to nutrients is still fragmentary. This was the question addressed in the present study. METHODS: After 24 h culture adult pig islets were perifused ...

Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients and that this may be explained ...

INTRODUCTION: The use of xenogenic islet cells may be a possibility to overcome the shortage of human donor organs to treat diabetes. Microencapsulation seems to be a promising method for immunoprotection. Since isolation, purification, encapsulation, and transplantation of islet cells are labor intensive, cryopreservation has emerged as an attractive system ...

In 2004, the human islet amyloid polypeptide (HIP) rat model was created by transfecting the Sprague-Dawley rat with the human islet amyloid polypeptide (hIAPP)-amylin gene. The objective of this study is to utilize the transmission electron microscope to study the longitudinal cellular and extracellular morphological changes within the islets of ...

OBJECTIVE: Autologous islet transplantation has been reported to show favorable outcomes on glucose metabolism. The objective of this study was to describe successful delivery of twins in an islet recipient who had undergone distal pancreatectomy. PATIENT: A 35-year-old woman who underwent distal pancreatectomy owing to a solid pseudopapillary neoplasm received ...

Human blood stem cell-derived insulin-producing cells can be easily isolated from autologous blood based on their unique phenotype. They act as pancreatic islet beta-cell progenitors, as demonstrated by authentic insulin production and homing to diabetic pancreatic islets. Clinical application of these autologous blood-derived insulin-producing cells holds great promise for diabetic ...

Arachidonic acid (AA) is generated in pancreatic beta-cells through the activation of Ca2+-dependent cytosolic phospholipase A2 (cPLA2) and the consequent hydrolysis of membrane phospholipids in the sn-2 position of the glycerophospholipid backbone. AA acts as a second messenger in beta-cells to elevate cytosolic Ca2+ levels and stimulate insulin secretion, but ...

We hypothesized that roasted Glycyrrhizae Radix (Glycyrrhizin Radix Praeparata, GRP) might modify anti-diabetic action due to compositional changes. Then we examined the anti-diabetic effect and mechanism of raw Glycyrrhizae Radix (GR) and GRP extracts and their major respective components, glycyrrhizin and glycyrrhetinic acid. In partial pancreatectomized (Px) diabetic mice, both ...

BACKGROUND: Fibrin glue has proven to be a good delivery system for cell transplantation but the factors that influence the fibrin-cell relationships are not well understood. The purpose of this study was to assess the effect of different concentrations of fibrin glue components (thrombin and fibrinogen) on the function of ...

Glucokinase activity is increased in pancreatic islets during pregnancy and in vitro by prolactin (PRL). The underlying mechanisms that lead to increased glucokinase have not been resolved. Since glucose itself regulates glucokinase activity in beta-cells, it was unclear whether the lactogen effects are direct or occur through changes in glucose ...

Mechanism of most of herbal used for diabetes mellitus treatment has not been well defined. This study was performed to investigate hypoglycemic effect of walnut leaf (Juglans regia L.   ), coriander leaf (Coriandrum sativum   L.) or pomegranate seed (Punica granatum L.   ), and their possible role on ...

Recent success in pancreatic islet transplantation has energized the field to discover an alternative source of stem cells with differentiation potential to beta cells. Generation of glucose-responsive, insulin-producing beta cells from self-renewing, pluripotent human ESCs (hESCs) has immense potential for diabetes treatment. We report here the development of a novel ...

Obesity is frequently associated with the consumption of high carbohydrate/fat diets leading to hyperinsulinemia. We have demonstrated that soy protein (SP) reduces hyperinsulinemia, but it is unclear by which mechanism. Thus, the purpose of the present work was to establish whether SP stimulates insulin secretion to a lower extent and/or ...

CONTEXT: The majority of islet transplant recipients experience a gradual decline in islet graft function, but the identification of islet-specific immune responses remains uncommon. OBJECTIVES: The aim was to present a case in which decline in islet graft function was accompanied by the appearance of islet donor-specific alloantibodies and demonstrate ...

Neuropeptides from the endocrine pancreas (the islets of Langerhans) play an important role in the regulation of blood glucose levels. Therefore, our aim is to identify the "peptidome" (the in vivo peptide profile at a certain time) of the pancreatic islets, which is beneficial for medical progress related to the ...

Augmented glucose-stimulated insulin secretion (GSIS) is an adaptive mechanism exhibited by pancreatic islets from insulin-resistant animal models. Gap junction proteins have been proposed to contribute to islet function. As such, we investigated the expression of connexin 36 (Cx36), connexin 43 (Cx43), and the glucose transporter Glut2 at mRNA and protein ...

BACKGROUND: It is known that males are more susceptible to develop type 2 diabetes than females. Estrogen has a protective effect on pancreatic islet against toxic agent such as amyloid. The role of estrogen in protection pancreatic islet against high glucose is still unknown. OBJECTIVE: Administration of estrogen in an ...

In order to alleviate the shortage of human donors, the use of porcine islets of Langerhans for xenotransplantation in diabetic patients has been proposed as a solution. To overcome rejection, we have developed a procedure for protecting the islets by combining them with Sertoli cells and placing them in a ...

Studies on rats with experimental diabetes induced by administration of alloxan showed that transcranial electrostimulation of endorphinergic brain structures stimulates the regeneration of damaged beta-cells in pancreatic islets of Langerhans. This was identified on pancreatic sections stained with hematoxylin and eosin. De novo formation of small islets was noted, as ...

Desmodium gangeticum is widely used in the indigenous system of medicine in India and is reported to contain flavone and isoflavonoid glycosides. It forms the ingredient of many Ayurvedic formulations used for diabetes. The present study was thus aimed at evaluating the insulin secretion and antidiabetic activity of Desmodium gangeticum. ...