Das Amyloid der Langerhansschen Inseln und seine Beziehung zum Diabetes mellitus<sup>*</sup>
          <sup>1</sup>

Schneider, Hartmut; Störkel, Stephan; Will, W.

doi:10.1055/s-2008-1070828

Cited by 57 publications

(14 citation statements)

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“…Amyloid deposition in T2D islets is localized to the perivascular space (de Koning et al 1994;Narita et al 1992;Schneider et al 1980) and is associated with increased β cell apoptosis and β cell loss (Jurgens et al 2011). In this study, islet amyloid was present in 8/9 diabetic subjects (comprising, on average, 14% ± 4% of islet area).…”

Section: Association Between Fragmentation Of Islet Capillaries and Amentioning

confidence: 53%

“…This is due to both functional abnormalities in the β cell, which manifests as impaired insulin release (Porte 1991), and decreased β cell mass (Butler et al 2003;Jurgens et al 2011;Klöppel et al 1985;Rahier et al 2008). Islet amyloid, similar to collagen deposition (Hayden et al 2008), is found in the extracellular matrix that lies between β cells and islet capillaries (de Koning et al 1994;Narita et al 1992;Schneider et al 1980,). However, our understanding of the mechanisms of β cell loss and dysfunction in diabetes remain incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

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Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes

Shostak

Fligner

Revetta

et al. 2015

J Histochem Cytochem.

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Human and rodent islets differ substantially in several features, including architecture, cell composition, gene expression and some aspects of insulin secretion. Mouse pancreatic islets are highly vascularized with interactions between islet endothelial and endocrine cells being important for islet cell differentiation and function. To determine whether human islets have a similar high degree of vascularization and whether this is altered with diabetes, we examined the vascularization of islets from normal human subjects, subjects with type 2 diabetes (T2D), and normal mice. Using an integrated morphometry approach to quantify intra-islet capillary density in human and mouse pancreatic sections, we found that human islets have five-fold fewer vessels per islet area than mouse islets. Islets in pancreatic sections from T2D subjects showed capillary thickening, some capillary fragmentation and had increased vessel density as compared with non-diabetic controls. These changes in islet vasculature in T2D islets appeared to be associated with amyloid deposition, which was noted in islets from 8/9 T2D subjects (and occupied 14% ± 4% of islet area), especially around the intra-islet capillaries. The physiological implications of the differences in the angioarchitecture of mouse and human islets are not known. Islet vascular changes in T2D may exacerbate β cell/islet dysfunction and β cell loss.

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Section: Association Between Fragmentation Of Islet Capillaries and Amentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes

Shostak

Fligner

Revetta

et al. 2015

J Histochem Cytochem.

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“…It was thought that these insoluble mature hIAPP amyloid deposits cause pancreatic beta-cell loss since amyloid deposits were found in the majority of individuals with type 2 diabetes [32–34]. Furthermore the extent of extracellular amyloid deposition correlated with beta-cell apoptosis and beta-cell loss [35] as well as clinical severity of the diabetes [36]. However, several recent studies suggested that it is soluble hIAPP oligomers rather than insoluble amyloid deposits that represent the main cytotoxic species [2, 37–41].…”

Section: Discussionmentioning

confidence: 99%

Degradation of islet amyloid polypeptide by neprilysin

et al. 2012

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Aims/hypothesis A progressive loss of pancreatic beta-cell function, a decrease in beta-cell mass, and accumulation of islet amyloid is characteristic of type 2 diabetes mellitus. The main constituent of islet amyloid is islet amyloid polypeptide. In this study we have examined the ability of the peptidase neprilysin to cleave human islet amyloid polypeptide and to prevent islet amyloid polypeptide induced pancreatic beta-cell toxicity. Methods Neprilysin and a catalytically compromised neprilysin mutant were tested for their ability to inhibit human islet amyloid polypeptide fibrillization and human islet amyloid polypeptide induced pancreatic beta-cell cytotoxicity. Degradation of human islet amyloid polypeptide by neprilysin was followed by high pressure liquid chromatography and the degradation products identified by mass spectrometry. Results Neprilysin prevents islet amyloid fibrillization by cleaving islet amyloid polypeptide at Arg11-Leu12, Leu12-Ala13, Asn14-Phe15, Phe15-Leu16, Asn22-Phe23 and Ala25-Ile26. In addition neprilysin also appears to prevent human islet amyloid polypeptide fibrillization through a non-catalytic interaction. Neprilysin protected insulinoma cells from exogenously added or endogenously expressed human islet amyloid polypeptide induced beta-cell cytotoxicity. Conclusions/interpretation Our data supports a potential therapeutic role for neprilysin in preventing type 2 diabetes mellitus. This study further supports the hypothesis that extracellular human islet amyloid polypeptide contributes to human islet amyloid polypeptide-induced beta-cell cytotoxicity. Whether human islet amyloid polypeptide works through a totally extracellular mechanism or through a cellular reuptake mechanism is unclear at this time.

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“…It has been proposed that overexpression of IAPP contributes to pancreatic amyloid formation and development of T2DM, this viewpoint supported by transgenic mouse and rat studies involving the overexpression of human IAPP (hIAPP) in islets of Langerhans [ 5 ]. Clinical studies indicate that hIAPP preferentially forms the amyloid deposition that implicates the pathology of islet hyalinization which is the pathological characteristic of T2DM [ 6 – 8 ]. Amyloid deposition is observed not only in patients with T2DM but also in some overweight or non-diabetic individuals [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo

Gao

Wang

et al. 2018

Lipids Health Dis

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BackgroundThe fibrillation of islet amyloid polypeptide (IAPP) triggered the amyloid deposition, then enhanced the loss of the pancreatic islet mass. However, it is not clear what factor is the determinant in development of the fibril formation. The aim of this study is to investigate the effects of lipid on IAPP fibril and its injury on pancreatic islet.MethodsThe fibril form of human IAPP (hIAPP) was tested using thioflavin-T fluorescence assay and transmission electron microscope technology after incubated with palmitate for 5 h at 25 °C. The cytotoxicity of fibril hIAPP was evaluated in INS-1 cells through analyzing the leakage of cell membrane and cell apoptosis. Type 2 diabetes mellitus (T2DM) animal model was induced with low dose streptozotocin combined the high-fat diet feeding for two months in rats. Plasma biochemistry parameters were measured before sacrificed. Pancreatic islet was isolated to evaluate their function.ResultsThe results showed that co-incubation of hIAPP and palmitate induced more fibril form. Fibril hIAPP induced cell lesions including cell membrane leakage and cell apoptosis accompanied insulin mRNA decrease in INS-1 cell lines. In vivo, Plasma glucose, triglyceride, rIAPP and insulin increased in T2DM rats compared with the control group. In addition, IAPP and insulin mRNA increased in pancreatic islet of T2DM rats. Furthermore, T2DM induced the reduction of insulin receptor expression and cleaved caspase-3 overexpression in pancreatic islet.ConclusionsResults in vivo and in vitro suggested that lipid and IAPP plays a synergistic effect on pancreatic islet cell damage, which implicated in enhancing the IAPP expression and accelerating the fibril formation of IAPP.

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Das Amyloid der Langerhansschen Inseln und seine Beziehung zum Diabetes mellitus^* ¹

Cited by 57 publications

References 0 publications

Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes

Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes

Degradation of islet amyloid polypeptide by neprilysin

Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo

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Das Amyloid der Langerhansschen Inseln und seine Beziehung zum Diabetes mellitus* 1

Cited by 57 publications

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Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes

Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes

Degradation of islet amyloid polypeptide by neprilysin

Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo

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Das Amyloid der Langerhansschen Inseln und seine Beziehung zum Diabetes mellitus^* ¹