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Imaging endoplasmic reticulum calcium with a fluorescent biosensor in transgenic mice.

The use of biosynthetic fluorescent sensors is an important new approach for imaging Ca(2+) in cells. Genetically encoded indicators based o … th mouse insulin I promoter. YC3.3er protein expression was limited to pancreatic beta-cells within islets of Langerhans and absent in the exocrine pancreas and other tissues. Animals developed and matured normally; sensor expression was unaffected by age. Glucose tolerance in transgenic mice was also unaffected, indicating the transgenic biosensor did not impair endo …

The role of clusterin on pancreatic beta cell regeneration after exendin-4 treatment in neonatal streptozotocin administrated rats.

We investigated the effects of exendin-4 (Ex4) treatment on expression of clusterin and β cell regeneration in the endocrine pancreas in neo … group, BrdU/insulin and insulin/clusterin immunopositive cells were significantly increased in the islets of Langerhans in comparison to the other groups. The areas occupied by the insulin mRNA and peptide positive cells and also pdx-1 immunopositive cells were decreased in the n2-STZ diabetic group compared with the other groups. The clusterin mRNA and protein posit …

The transplanted fetal endocrine pancreas undergoes an inherent sequential differentiation similar to that in the native pancreas. An ultrastructural study in the pig-to-mouse model.

This study examines, at the ultrastructural level, whether the fetal porcine endocrine pancreas (insulin, glucagon, somatostatin, and pancreatic polypeptide [PP]- and islet amyloid polypeptide [IAPP]-containing cells) develops normally after transplantation under the kidney capsule in athymic mice. We have thus used an in vivo pig-to-mouse model for the differentiation of the endocrine pancreas removed from its normal milieu. Islet-like cell clusters (ICCs) were prepared from the fetal porcine pancreas as previously described and transplanted under the renal capsule of athymic mice. At various

Stem cells and regenerative medicine for diabetes mellitus.

A profound knowledge of the development and differentiation of pancreatic tissues, especially islets of Langerhans, is necessary for developing regenerative therapy for severe diabetes mellitus. A recent developmental study showed that PTF-1a is expressed in almost all parts of pancreatic tissues, in addition to PDX-1, a well-known transcription factor that is essential for pancreas development. Another study suggested that alpha cells and beta cells individually, but not sequentially, differentiated from neurogenin-3--expressing precursor cells. Under strong induction of pancreas regeneration…

Интерферон-гамма имеет важное значение для уничтожения бета-клеток и развития сахарного диабета с инсулиновой зависимостью.

Аутоиммунное разрушение бета-элементов островов Лангерхана ведет к инсулиннозависимому сахарному диабету (IDDM). Трансгенные мыши (LCMV), которые выражают нуклеопротеин (NP) или гликпротеин (GP) LCMV под контролем RIP в их бета-элементах, разрабатывают IDDM после инфекции с LCMV и служат моделью для IDDM с вирусом. Недавно Каги и др. (Каги, Д., Б. Одерматт, П. Охаши, Р.М. Зинкернагейл и Х. Хенгартнер, 1996, Дж. Эксп. Мед. 183:2143-2149 показал, используя RIP LCMV perforin-definente mice, что IDDM не происходит при отсутствии перфорина. Они пришли к выводу о том, что цитотоксичные лимфоциты (КТ

Совпадение в аннотации оригинала
Autoimmune mediated destruction of beta cells of the islets of Langerhans leads to insulin-dependent diabetes mellitus (IDDM). Rat insulin promoter (RIP) lymphocytic choriomeningitis virus (LCMV) transgenic mice that express the nucleoprotein (NP) or glycoprotein (GP) of LCMV under control of the RIP in their beta cells develop IDDM after infection with LCMV…

Development of novel 67/68Ga-labeled pyridyl benzofuran derivatives as islet amyloid imaging probes.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) accounts for the majority of diabetes mellitus cases, and β-cell function and mass may be involved in its pathophysiology. The deposition of islet amyloid in pancreas islets is one of the mechanisms of progression of T2DM. Therefore, the development of imaging techniques for islet amyloid deposition contributes to the early-phase diagnosis and elucidation of the pathogenic mechanism of T2DM. We have reported that pyridyl benzofuran (PBF) is a promising scaffold for islet amyloid imaging probes. In this study, we designed [67/68Ga]Ga-dedpa-(PBF)2, w

Linking hIAPP misfolding and aggregation with type 2 diabetes mellitus: a structural perspective.

There are over 40 identified human disorders that involve certain proteins folding incorrectly, accumulating in the body causing damage to cells and organs and causing disease. Type 2 Diabetes Mellitus (T2DM) is one of these protein misfolding disorders (PMDs) and involves human islet amyloid polypeptide (hIAPP) misfolding and accumulating in parts of the body, primarily in the pancreas, causing damage to islet cells and affecting glucose regulation. In this review, we have summarised our current understanding of what causes hIAPP to misfold, what conformations are found in different parts of

Islet amyloid: a long-recognized but underappreciated pathological feature of type 2 diabetes.

Islet amyloid has been recognized as a pathological entity in type 2 diabetes since the turn of the century. It has as its unique component the islet beta-cell peptide islet amyloid polypeptide (IAPP), or amylin, which is cosecreted with insulin. In addition to this unique component, islet amyloid contains other proteins, such as apolipoprotein E and the heparan sulfate proteoglycan perlecan, which are typically observed in other forms of generalized and localized amyloid. Islet amyloid is observed at pathological examination in the vast majority of individuals with type 2 diabetes but is rare

Defining the transcriptional and cellular landscape of type 1 diabetes in the NOD mouse.

Our ability to successfully intervene in disease processes is dependent on definitive diagnosis. In the case of autoimmune disease, this is particularly challenging because progression of disease is lengthy and multifactorial. Here we show the first chronological compendium of transcriptional and cellular signatures of diabetes in the non-obese diabetic mouse. Our data relates the immunological environment of the islets of Langerhans with the transcriptional profile at discrete times. Based on these data, we have parsed diabetes into several discrete phases. First, there is a type I interferon…

A sporadic case of Ehlers-Danlos syndrome type IV: diagnosed by a morphometric study of collagen content.

A sporadic case of a young woman with Ehlers-Danlos syndrome (EDS) type IV is described. Multiple aneurysms of medium-sized arteries were noted. Histological study revealed deposition of acid mucopolysaccharides in the media of major arteries and in the intima of smaller arteries with intimal thickening. Systemic changes related to stenosis were observed in arteries more than 100 microns in diameter. Histologic study revealed hyperplasia of adipocytes in the submucosal layer of the intestines and the trachea, and fibrosis of Langerhans' islets of the pancreas. Typical signs for EDS such as ski

[Amylin under examination. Fibrillogenic polypeptide hormone of the pancreas].

In patients or animals affected by type 2 diabetes mellitus (DM2, non-insulin dependent diabetes mellitus [NIDDM]) some pathological deposits, called amyloid, are observed among cells of islets of Langerhans. Among other constituents, deposits consist of an insoluble, fibrillar form of peptide neurohormone called amylin, produced by pancreatic beta cells. It is thought that formation of fibrillar deposits of misfolded and aggregated peptide is highly toxic to beta cells and leads to cell dysfunction, cell loss, pancreas destruction and progress of the disease. This relatively small 37-amino ac…

Insulin secretion during acid-base alterations. III: Role of extracellular calcium on the blocking effect of alkalosis.

Insulin secretion by the perfused rat pancreas and incubated islets of Langerhans challenged with glucose is hampered under metabolic alkalosis. In order to assess if the alteration was due to changes in extracellular ionic calcium availability at pH 7.8, perfusion and incubation media of different composition were used. Since sodium bicarbonate and bovine serum albumin diminish the ionic calcium concentration with a pH increase, they were substituted in the buffers by Hepes or dextran, respectively. Moreover, with the aid of ionic calcium measurement, its concentration was corrected in the pH…

Virus-induced autoimmunity: monoclonal antibodies that react with endocrine tissues.

Mice infected with reovirus type 1 develop an autoimmune polyendocrine disease. Spleen cells from these mice were fused with myeloma cells and the culture fluids were screened by indirect immunofluorescence for autoantibodies reactive with normal mouse tissues. A large panel of cloned, stable antibody-producing hybridomas has been obtained. Fourteen of the hybridomas make autoantibodies that react with cells in the islets of Langerhans, 24 with cells in the anterior pituitary, 11 with cells in gastric mucosa, and 5 with nuclei. Except for the antibodies to nuclei, the monoclonal autoantibodies…

Feline insular amyloid: histochemical distinction from secondary systemic amyloid.

Amyloid in islets of Langerhans from 48 domestic cats, one human, one non-human primate, and one raccoon was compared with secondary systemic amyloid from three domestic cats, one dog, one human, and one cow to determine affinity for Congo red dye after treatment of paraffin-embedded tissue sections with potassium permanganate and dilute sulfuric acid. Insular amyloid from all six species was resistant to pretreatment with potassium permanganate, i.e., affinity for Congo red was retained, whereas secondary systemic amyloid from all species was sensitive to the potassium permanganate pretreatme…

An international consensus on screening and monitoring early-stage type 1 diabetes: A roadmap to European implementation.

Type 1 diabetes (T1D) is a chronic autoimmune disease that results in loss of insulin-secreting pancreatic β-cells in the islets of Langerhans. A diagnosis of T1D is typically associated with children and adolescents, yet half of all diagnoses of T1D are made in adults. In children and adolescents, T1D is often first recognized following hospitalization for diabetic ketoacidosis (DKA), which occurs in approximately 20%-50% of new-onset T1D for people younger than 18 years of age in Europe. For adults with new-onset T1D, DKA rates of up to 24% are estimated. Early-stage T1D, during the asymptom…

Immunological markers in type 1 diabetes mellitus in Thi-Qar province, southern Iraq.

Type 1 diabetes mellitus (T1D) is a chronic autoimmune illness defined as insulin insufficiency resulting from the autoimmune breakdown of pancreatic beta cells producing insulin in the islets of Langerhans. Biomarkers are markers of physiological or pathological processes that are normal or abnormal, playing a crucial function in clinical evaluation, prognosis, and therapy response monitoring. This study aimed to investigate some biomarkers associated with T1D and examine the association between glutamic acid carboxylase (GADA) antibody and islet antigen-2 autoantibody (IA-2A) for β-cell stre…

Novel techniques of pancreas and islet preservation.

PURPOSE OF REVIEW: In recent years, rates of pancreas transplantation have remained stagnant in part due to increasingly stringent donor criteria. Compared to other abdominal organs, the use of extended criteria grafts in pancreas transplantation, including donation after cardiac death (DCD) donors, remains limited. The purpose of this review is to highlight recent work in the field of pancreas and islet preservation. RECENT FINDINGS: Emerging preclinical and clinical data support the use of machine perfusion, both normothermic and hypothermic, as a mechanism by which to assess graft viabilit