1,721,093 research outputs found
Probing the light scattering properties of insulin secretory granules in single live cells
No full textLight scattering was recently demonstrated to serve as an intrinsic indicator for pancreatic islet cell mass and secretion. The insulin secretory granule (ISG), in particular, was proposed to be a reasonable candidate as the main intracellular source of scattered light due to the densely-packed insulin semi-crystal in the granule lumen. This scenario, if confirmed, would in principle open new perspectives for label-free single-granule imaging, tracking, and analysis. Contrary to such expectations, here we demonstrate that ISGs are not a primary source of scattering in primary human β-cells, as well as in immortalized β-like cells, quantitatively not superior to other intracellular organelles/structures, such as lysosomes and internal membranes. This result is achieved through multi-channel imaging of scattered light along with fluorescence arising from selectively-labelled ISGs. Co-localization and spatiotemporal cross-correlation analysis is performed on these signals, and compared among different cell lines. Obtained results suggest a careful re-thinking of the possibility to exploit intrinsic optical properties originating from ISGs for single-granule imaging purposes
From genotype to human ß cell phenotype and beyond
No full textPolygenic type 2 diabetes mellitus (T2DM) is a multi-factorial disease due to the interplay between genes and the environment. Over the years, several genes/loci have been associated with this type of diabetes, with the majority of them being related to β cell dysfunction. In this review, the available information on how polymorphisms in T2DM-associated genes/loci do directly affect the properties of human islet cells are presented and discussed, including some clinical implications and the role of epigenetic mechanisms
The pancreatic beta cells in human type 2 diabetes
No full textBell-cell (beta-cell) impairment is central to the development and progression of human diabetes, as a result of the combined effects of genetic and acquired factors. Reduced islet number and/or reduced beta cells amount in the pancreas of individuals with Type 2 diabetes have been consistently reported. This is mainly due to increased beta cell death, not adequately compensated for by regeneration. In addition, several quantitative and/or qualitative defects of insulin secretion have been observed in Type 2 diabetes, both in vivo and ex vivo with isolated islets. All this is associated with modifications of islet cell gene and protein expression. With the identification of several susceptible Type 2 diabetes loci, the role of genotype in affecting beta-cell function and survival has been addressed in a few studies and the relationships between genotype and beta-cell phenotype investigated. Among acquired factors, the importance of metabolic insults (in particular glucotoxicity and lipotoxicity) in the natural history of beta-cell damage has been widely underlined. Continuous improvements in our knowledge of the beta cells in human Type 2 diabetes will lead to more targeted and effective strategies for the prevention and treatment of the disease
A role for autophagy in ß-cell life and death
No full textAutophagy is a vacuolar, self-digesting mechanism responsible for the removal of organelles and defined regions of the cytoplams. This process has, in general, a beneficial role for the cell, since it regulates the turnover of aged proteins and eliminates damaged structures. However, cells that undergo altered autophagy may be triggered to die in a non-apoptotic manner. As a matter of fact, in recent years it has become clear that dysregulated autophagy may be implicated in several disorders, such as cancer, neurodegenerative diseases and hepatic encephalopathy. We have recently shown that beta-cells of type 2 diabetic subjects show signs of autophagy associated death, which may contribute to the overall loss of beta-cell mass in type 2 diabetes. In addition, studies with cell lines and rodent models have demonstrated the importance of autophagy in beta-cell function and survival. Altogether, the available evidence supports the view that autophagy is implicated in beta-cell pathophysiology, and suggests that addressing the molecular mechanisms involved in autophagic regulation might provide clues for preventing or treating beta-cell damage in diabetes
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Ultrastructural Alterations of Beta Cells in Human Type 1 and Type 2 Diabetes Mellitus
No full textBoth types of diabetes are characterized by progressive beta-cell failure and death, leading to absolute or relative insulin deficiency. To date, very limited information is available about the ultrastructural alterations of beta cells in human diabetes. We performed morphological and morphometric electron microscopy evaluation of pancreatic islet cells obtained from 5 non-diabetic (ND), 5 type 1 (T1D) and 5 type 2 (T2D) diabetic organ donors, with similar clinical features. The total number of islet cells examined was 954 in ND, 646 in T1D and 820 in T2D. A lower amount of beta cells was found in both T1D and T2D than in ND islets (57±3 and 47±4 vs. 69±2%, p<0.01), whereas no differences were observed for delta cells; alpha cells were increased (34.8±1.1 vs 24.8±1.8%, p<0.05) only in T2D. In both T1D and T2D more beta cells showed signs of apoptosis than in ND (6.8±2.0 and 9.3±2.3 vs. 2±1.3%, p<0.01). Insulin granules were less represented in T2D than in ND beta cells (3.1±0.5 vs. 8.7±1.1ml%, p<0.01), whereas no significant changes were found in T1D. Volume density of the endoplasmic reticulum was increased in T2D and unchanged in T1D samples (2.8±0.5, p<0.01, and 1.2±0.2 vs. 0.7±0.2 ml%); mitochondria number and volume (9.1±1.1 vs. 5.8±0.4 ml%) were also higher (both p<0.01) in T2D than in ND beta cells, whereas no significant differences were found in T1D. Finally, in the peri-insular infiltrate we found a higher number of macrophages (4.2±0.8 vs 1.0±0.2 cells/islet, p<0.01) in T2D and an increased number of mast cells (1.8±0.3 vs 0.5±0.2 cells/islet, p<0.01) in T1D. These results show that in each type of diabetes, beta cells have specific ultrastructural alterations, as cause or consequence of functional and survival defects; targeting the deranged organelles might improve the outcome of therapeutic interventions
Ultrastructural morphometric analysis of insulin secretory granules in human type 2 diabetes.
Full text linkWe performed an ultrastructural morphometric analysis of insulin secretory
granules in pancreatic beta cells from control and type 2 diabetic multiorgan
donors. The volume density of insulin granules significantly (p < 0.05) reduced
in beta cells from type 2 diabetic patients with respect to non-diabetic
subjects, and this reduction was mainly attributable to a decrease in mature
granules. On the contrary, no significant difference was observed in the volume
density of docked granules between controls and type 2 diabetic patients. In
addition, there was a significant positive correlation between the density volume
of total insulin granules and stimulated insulin secretion in non-diabetic
islets. In conclusion, we detected significant changes in the intracellular
distribution of insulin secretory granules within the beta cell that might be
related with the alterations in insulin secretion observed in type 2 diabetes
patients
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