Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal ...

This manuscript reports the application of the selective-withdrawal coating technique to the microencapsulation of insulin-producing pancreatic islets within thin poly(ethylene glycol) coatings. These polymer coatings permit the islets to respond to changes in glucose concentration by producing insulin with a dose-response profile that is substantially similar to that of unencapsulated ...

OBJECTIVES: We examined how lipotoxicity contributes to pancreatic beta-cell secretory dysfunction. METHODS: Effects of palmitate (0.2 mmol/L) were assessed on insulin secretion and soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery in isolated pancreatic islets of type 2 diabetic Goto-Kakizaki (GK) rats and control Wistar (W) rats. RESULTS: One-day palmitate ...

Many hypoglycemic and hyperglycemic episodes associated with clinical use of gatifloxacin (GFLX), a novel fluoroquinolone antimicrobial agent, have been reported in recent years. Some have reported hypoglycemia induced by fluoroquinolones, indicating that these agents may stimulate insulin secretion from pancreatic islet cells. In this study, we investigated the effect of ...

A current model ascribes glucose-induced insulin secretion to the interaction of a triggering pathway (K(ATP) channel-dependent Ca(2+) influx and rise in cytosolic [Ca(2+)](c)) and an amplifying pathway (K(ATP) channel-independent augmentation of secretion without further increase of [Ca(2+)](c)). However, several studies of sulfonylurea receptor 1 null mice (Sur1KO) failed to measure ...

BACKGROUND: The effects of sirolimus on insulin secretion are still debated. Our aim was to investigate the effects of sirolimus, both (1) in vivo in healthy minipigs; and (2) in vitro on human islets. METHODS: (1) Ten minipigs were evaluated during three successive stages: (a) basal; (b) at the end ...

To present a case of an elderly man with noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) and to determine the pathogenesis of this syndrome. The pancreas of our patient with NIPHS was immunocytochemically stained for insulin-, glucagon-, and somatostatin-secreting cells and pancreatic and duodenal homeobox protein (PDX-1). The clinical findings and morphologic ...

Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Although traditional insulin therapy has alleviated the short-term effects, long-term complications are ubiquitous and harmful. For these reasons, alternative treatment options are being developed. This review investigates one appealing area: cell replacement using encapsulated islets. Encapsulation ...

Isolated islets of Langerhans have been widely used to clarify the beta-cell function and insulin secretion in normal and diabetic states. Most of these studies have applied a pooled-islet design using isolated islets from a number of animals. However, to our knowledge, no previous studies have explored the consequences of ...

Transplantation of pancreatic islets is a promising therapeutic treatment for type 1 diabetes mellitus. For clinical and experimental transplantation, a large number of pure pancreatic islets are required for transplantation. Thus, the improvement of islet isolation and purification techniques are crucial. In this context, iodixanol-based solution, successfully used for the ...

This review highlights some recent developments and diversified applications of islets in diabetes research as they are rapidly emerging as a model system in biomedical and biotechnological research. Isolated islets have formed an effective in vitro model in antidiabetic drug development programme, screening of potential hypoglycaemic agents and for investigating ...

Diabetes mellitus results from inadequate insulin action, which can be viewed as a consequence of the limited ability to restore beta cells after they are lost as the result of metabolic exhaustion, autoimmune destruction, or surgical insult. Arguably, a uniformly effective therapeutic pathway to address all forms of diabetes would ...

BACKGROUND: The long-term viability and function of transplanted encapsulated neonatal porcine islets was examined in a diabetic patient. METHODS AND RESULTS: A 41-yr-old Caucasian male with type 1 diabetes for 18 yr was given an intraperitoneal transplant of alginate-encapsulated porcine islets at the dose of 15,000 islet equivalents (IEQs)/kg bodyweight ...

AIM: To investigate the influence of heme oxygenase-1 (HO-1) gene transfer on the viability and function of cultured rat islets in vitro. METHODS: Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with ...

Betagranin, an N-terminal fragment of chromogranin A, results from a proteolytic processing, and is co-secreted with insulin. While other chromogranin A-derived peptides negatively modulate hormone secretion, the role of betagranin in pancreatic beta-cells is so far unknown. We have recently shown that pancreatic islet betagranin levels are down-regulated in obese, ...

AIM: To investigate the effect of chitooligosaccharides on proliferation of pancreatic islet cells, release of insulin and 2 h plasma glucose in streptozotocin-induced diabetic rats. METHODS: In vitro, the effect of chitooligosaccharides on proliferation of pancreatic islet cells and release of insulin was detected with optical microscopy, colorimetric assay, and ...

A microfluidic chip that allows for the continuous monitoring of cellular secretions from multiple independent living samples was developed. Performance of the device was characterized through the analysis of insulin secretion from islets of Langerhans. The chip contained four individual channel networks, each capable of performing electrophoresis-based immunoassays of the ...

Large clinical trials have shown that inhibition of the renin-angiotensin system (RAS) can delay and/or prevent the onset of Type 2 diabetes mellitus (T2DM) in high-risk individuals, such as those with hypertension or chronic heart failure. Moreover, a meta-analysis of these randomized clinical studies concluded that the mean weighted relative ...

In order to elucidate a possible relationship between beta-cell function and conversion of proinsulin to insulin, isolated rat pancreatic islets were maintained in tissue culture for 1 week at various glucose concentrations (5 x 6-56 mM). Studies were also conducted on islets cultured for 48 h with interleukin-1beta (IL-1beta). By ...

The role of recipient hyperglycemia on timing of allograft survival is unknown. In this study, we investigated if and how variation in recipient glycemia affects the ability to achieve and maintain normoglycemia after transplant of C57BL/6 islets into diabetic BALB/c mice. 85 diabetic BALB/c mice with non-fasting glycaemia ranging between ...

Success in islet-transplantation-based therapies for type I diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Embryonic stem cells (ESCs) have been successfully induced into insulin producing islet-like structure in several studies. However, the source of the ESCs has presented ...

BACKGROUND: Islet transplantation can reduce or eliminate the need for insulin in patients with type 1 diabetes. Exenatide is a long acting analogue of Glucagon-like peptide-1 (GLP-1) that augments glucose induced insulin secretion, and may increase beta cell mass. We evaluated the effect of exenatide on insulin secretion after islet ...

We measured the impact of chronic late gestation hypoglycemia on pancreatic islet structure and function to determine the cause of decreased insulin secretion in this sheep model of fetal nutrient deprivation. Late gestation hypoglycemia did not decrease pancreas weight, insulin content, beta-cell area, beta-cell mass, or islet size. The pancreatic ...

Immunohistochemical analysis was used to define the precise cell-specific localization of Glucose-6-phosphatase (Glc6Pase) and cytosolic form of the phosphoenolpyruvate carboxykinase (PEPCK-C) in the digestive system (liver, small intestine and pancreas) and the kidney. Co-expression of Glc6Pase and PEPCK-C was shown to take place in hepatocytes, in proximal tubules of the ...

There is a need for simple, quantitative and prospective assays for islet quality assessment that are predictive of islet transplantation outcome. The current state-of-the-art athymic nude mouse bioassay is costly, technically challenging and retrospective. In this study, we report on the ability of 2 parameters characterizing human islet quality: (1) ...

BACKGROUND: We previously reported that Chungkookjang (CKJ), fermented unsalted soybeans, exhibited better anti-diabetic action than cooked soybeans (CSB) in vitro, but its effectiveness and mechanism have not been studied in vivo. AIM OF THE STUDY: We investigated whether CKJ modulated insulin resistance, insulin secretion, and pancreatic beta-cell growth and survival ...

Islet amyloid contributes to the loss of beta-cell mass in type 2 diabetes. To examine the roles of glucose and time on amyloid formation, we developed a rapid in vitro model using isolated islets from human islet amyloid polypeptide (hIAPP) transgenic mice. Islets from hIAPP transgenic and non-transgenic mice were ...

Islet cell transplantation is a promising option for the restoration of normal glucose homeostatsis in patients with type-1 diabetes. But problems remain regarding the efficient use of donor cells and the prevention of graft rejection by the host immune system. Previously, we were able to show that xenotransplantation of microencapsulated ...

Chronic exposure of pancreatic islets to elevated plasma lipids ( lipotoxicity) can lead to beta-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase ( iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion ...

Diabetes is a chronic autoimmune disease that affects 4-5% of the world's population. If the present trends continue, diabetes would soon become a major/leading health problem worldwide. Hence there is an urgent need to develop novel approaches for the treatment of diabetes. While transplantation of the pancreas or that of ...

The roles played by arachidonic acid and its cyclooxygenase (COX)-generated and lipoxygenase (LOX)-generated metabolites have been studied using rodent islets and insulin-secreting cell lines, but very little is known about COX and LOX isoform expression and the effects of modulation of arachidonic acid generation and metabolism in human islets. We ...

The system that regulates insulin secretion from beta-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. As calcitonin gene-related peptide (CGRP)-expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP-containing primary sensory neurons is sensitive to capsaicin, the islet-innervating sensory fibers may represent the ...

Pancreatic islets isolated from adult obese rats, obtained by neonatal treatment with monosodium L-glutamate (MSG), oversecrete insulin stimulated by glucose concentration. Whereas adult MSG obese rats are hyperinsulinemic, their pancreatic islets still secrete insulin after high glucose demand. This is crucial so that the animals do not become hyperglycemic. Islets ...

Substitution of diseased organ/tissues with totally artificial machines or transplantable biohybrid devices where functionally competent cells are enveloped within immunoprotective artificial membranes could represent one of the future goals in medicine. In particular, artificial or, closer to feasibility, biohybrid artificial pancreas (BHAP) could replace the function of pancreatic islet beta-cells ...

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 pancreatic tissue. Diabetes mellitus was ...

OBJECTIVES: Diabetes is a serious health problem. It has been proposed that islet neogenesis from pancreatic progenitor cells may restore insulin secretion in diabetic mammals. Islet neogenesis- associated protein (INGAP) stimulates islet neogenesis; therefore, we hypothesized that it would stimulate islet neogenesis in dogs. METHODS: Forty nondiabetic beagle dogs were ...

Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts ...

Pravastatin, irbesartan and captopril are frequently used in the treatment of patients with Type 2 diabetes. These drugs also exert beneficial metabolic effects, causing an improved glucose tolerance in patients, but the precise mechanisms by which this is achieved remain elusive. To this end, we have studied whether these drugs ...

Thyrotropin Releasing Hormone (TRH), first identified in the hypothalamus as a regulator of the Pituitary-Thyroid axis, has also been found in the beta-cell of the pancreas co-localised with insulin. The significance of this association is emphasised by the report that the TRH knock-out (KO) mouse is hyperglycemic. These findings have ...

The ability to culture porcine islets for extended times allows for both their functional assessment and the assurance of their microbiological safety prior to transplantation. We have previously shown that agarose-encapsulated porcine islets can be cultured for at least 24 weeks. In the current study, porcine islet agarose macrobeads cultured ...

Insulin secretion from the 2,000-3,000 beta-cells in an islet is a highly synchronized activity with discharge of insulin in coordinate secretory bursts at approximately 4-min intervals. Insulin secretion progressively declines in type 2 diabetes and following islet transplantation. Both are characterized by the presence of islet amyloid derived from islet ...

Surprisingly, the effect of acute diabetes on immunity has not been examined in detail. We, herein, show for the first time that untreated acute diabetes causes rapid lymphopenia followed by homeostatic T-cell proliferation. The diabetes-induced lymphopenia was associated with an immunosuppressed state that could be sufficiently strong to allow engraftment ...

PURPOSE: Stem cell-derived tissue may provide a curative treatment for children with type 1 diabetes. Using an avian model, we have previously shown that foregut mesenchyme is able to differentiate into insulin-positive beta-cell islets (B islets). Successful clinical islet transplantation, however, is reliant on graft tissue containing both insulin- and ...

Islet Neogenesis-Associated Protein (INGAP) is a member of the Reg family of proteins implicated in various settings of endogenous pancreatic regeneration. The expression of INGAP and other RegIII proteins has also been linked temporally and spatially with the induction of islet neogenesis in animal models of disease and regeneration. Furthermore, ...

Pancreatic islets possess an autonomous mechanism of blood flow regulation, independent of that of the exocrine pancreas. To study islet vascular regulation without confounding effects of the exocrine blood vessels, we have developed a technique enabling us to isolate single pancreatic islets and then to perfuse them using their endogenous ...

While insulin replacement remains the cornerstone treatment for type I diabetes mellitus (T1DM), the transplantation of pancreatic islets of Langerhans has the potential to become an important alternative. And yet, islet transplant therapy is limited by several factors, including far too few donor pancreases. Attempts to expand mature islets or ...

CONTEXT: In patients with type 1 diabetes and reduced awareness of hypoglycemia, the glycemic thresholds for activation of counterregulatory hormone and symptom responses to hypoglycemia are impaired, in part due to recurrent episodes of hypoglycemia. Islet transplantation can ameliorate occurrences of hypoglycemia in these patients. OBJECTIVE: The objective of the ...

Insulin is both a hormone regulating energy metabolism and a growth factor. We and others have shown that physiological doses of insulin initiate complex signals in primary human and mouse beta-cells, but the functional significance of insulin's effects on this cell type remains unclear. In the present study, the role ...

Pax6, a paired homeodomain transcription factor, plays crucial roles in morphogenesis of eye, central nervous system, and pancreatic islets. Recently, heterozygosity for pax6 mutation has been reported in some individuals with glucose intolerance and aniridia. To investigate the role of pax6 for pancreatic islet function, we examined the pancreatic phenotype ...

The pancreatic beta-cell plays a central role in the maintenance of glucose homeostasis and in the pathogenesis of both type 1 and type 2 diabetes mellitus. Elucidation of the insulin secretory defects observed in diabetes first requires a better understanding of the complex mechanisms regulating insulin secretion, which are only ...