scholarly journals Association between Field Liming and the Epidemic of Type 1 Diabetes

2017 ◽  
Vol 4 (1) ◽  
pp. 27
Author(s):  
Seppo K Junnila
Keyword(s):  
Beta Cell ◽  
Large Scale ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Apoptosis ◽  
Coordination State ◽  
Native Form ◽  
Western Countries ◽  
Weathering Processes ◽  
Physiologic Form

Zinc is an essential nutrient for mammals. Zinc has only one oxidation state Zn2+ but it has many coordination states, which can alter without demanding energy. Coordination states depend on prevailing pH. In soils the coordination state changes from octahedral (nonphysiologic) form to tetrahedral (physiologic) form when pH rises to about 6.5. Weathering processes of common soil mineral mica are also pH dependent. Large scale argricultural field liming began from 1950's onward in the Western Countries and since that time the incidence of T1D began to increase in the Western Countries. Liming elevates soil pH often near 6.5 and favours mosaic mica-vermiculite nanoparticle formation in which vermiculite corner binds zinc in tetrahedral (physiological) coordination state. In this pH mica corner remains in native form and offers the plane for soluble pMHC  molecule (binded with antigenic beta-cell specific self peptide) to adhere on mica and as a  consequence to trigger the activation of autoreactive CD4 and/or CD8 T cells. Beta-cell specific autoantigens are released  because abundant zinc derived from endocytosed zinc-mica-vermiculite particles in lysosomes leads to incresed beta-cell apoptosis, also the physiological neonatal beta-cell mass remodeling enhance beta-cell specific auto-antigen release. Furthermore enterovirusinfections during first years of life are common and can release beta-cell specific auto-antigens.  The probable disease mechanism is dealt with this review article.

scholarly journals Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

2002 ◽  
Vol 174 (2) ◽  
pp. 225-231 ◽  
Author(s):  
H Del Zotto ◽  
CL Gomez Dumm ◽  
S Drago ◽  
A Fortino ◽  
GC Luna ◽  
...  
Keyword(s):  
Body Weight ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Serum Glucose ◽  
Beta Cell Apoptosis ◽  
Cell Replication ◽  
Replication Rate ◽  
Endocrine Tissue

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic beta-cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and beta-cell mass, beta-cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and beta-cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0.05) larger than that of the CD group (556.0+/-8.3 vs 470.0+/-13.1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0.05) in SRD than in CD rats (serum glucose, 8.11+/-0.14 vs 6.62+/-0.17; triacylglycerol, 1.57+/-0.18 vs 0.47+/-0.04). The number of pancreatic islets per unit area increased significantly (P<0.05) in SRD rats (3.29+/-0.1 vs 2.01+/-0.2). A significant increment (2.6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the beta-cell mass (P=0.0025). The islet cell replication rate, measured as the percentage of PCNA-labelled beta cells increased 6.8 times in SRD rats (P<0.03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0.03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of beta-cell mass induced by SRD was accomplished by an enhanced replication of beta cells together with a decrease in the rate of beta-cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.

scholarly journals Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Diego Balboa ◽  
Jonna Saarimäki-Vire ◽  
Daniel Borshagovski ◽  
Mantas Survila ◽  
Päivi Lindholm ◽  
...  
Keyword(s):  
Beta Cell ◽  
Er Stress ◽  
Cell Mass ◽  
Gene Mutations ◽  
Beta Cell Mass ◽  
Neonatal Diabetes ◽  
Beta Cell Apoptosis ◽  
Beta Cell Proliferation ◽  
Sequencing Analysis ◽  
Mtorc1 Signaling

Insulin gene mutations are a leading cause of neonatal diabetes. They can lead to proinsulin misfolding and its retention in endoplasmic reticulum (ER). This results in increased ER-stress suggested to trigger beta-cell apoptosis. In humans, the mechanisms underlying beta-cell failure remain unclear. Here we show that misfolded proinsulin impairs developing beta-cell proliferation without increasing apoptosis. We generated induced pluripotent stem cells (iPSCs) from people carrying insulin (INS) mutations, engineered isogenic CRISPR-Cas9 mutation-corrected lines and differentiated them to beta-like cells. Single-cell RNA-sequencing analysis showed increased ER-stress and reduced proliferation in INS-mutant beta-like cells compared with corrected controls. Upon transplantation into mice, INS-mutant grafts presented reduced insulin secretion and aggravated ER-stress. Cell size, mTORC1 signaling, and respiratory chain subunits expression were all reduced in INS-mutant beta-like cells, yet apoptosis was not increased at any stage. Our results demonstrate that neonatal diabetes-associated INS-mutations lead to defective beta-cell mass expansion, contributing to diabetes development.

scholarly journals MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis

2019 ◽  
Vol 11 (9) ◽  
pp. 747-760 ◽  
Author(s):  
Yunxia Zhu ◽  
Yi Sun ◽  
Yuncai Zhou ◽  
Yan Zhang ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Beta Cell ◽  
Er Stress ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Stress Conditions ◽  
Beta Cell Apoptosis ◽  
Induced Apoptosis

AbstractCurrent research indicates that beta cell loss in type 2 diabetes may be attributed to beta cell dedifferentiation rather than apoptosis; however, the mechanisms by which this occurs remain poorly understood. Our previous study demonstrated that elevation of microRNA-24 (miR-24) in a diabetic setting caused beta cell dysfunction and replicative deficiency. In this study, we focused on the role of miR-24 in beta cell apoptosis and dedifferentiation under endoplasmic reticulum (ER) stress conditions. We found that miR-24 overabundance protected beta cells from thapsigargin-induced apoptosis at the cost of accelerating the impairment of glucose-stimulated insulin secretion (GSIS) and enhancing the presence of dedifferentiation markers. Ingenuity® Pathway Analysis (IPA) revealed that elevation of miR-24 had an inhibitory effect on XBP1 and ATF4, which are downstream effectors of two key branches of ER stress, by inhibiting its direct target, Ire1α. Notably, elevated miR-24 initiated another pathway that targeted Mafa and decreased GSIS function in surviving beta cells, thus guiding their dedifferentiation under ER stress conditions. Our results demonstrated that the elevated miR-24, to the utmost extent, preserves beta cell mass by inhibiting apoptosis and inducing dedifferentiation. This study not only provides a novel mechanism by which miR-24 dominates beta cell turnover under persistent metabolic stress but also offers a therapeutic consideration for treating diabetes by inducing dedifferentiated beta cells to re-differentiation.

scholarly journals Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies

2021 ◽  
Vol 22 (10) ◽  
pp. 5303
Author(s):  
Safia Costes ◽  
Gyslaine Bertrand ◽  
Magalie A. Ravier
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Apoptosis ◽  
Chronic Hyperglycemia

Type 2 diabetes (T2D) is characterized by chronic hyperglycemia secondary to the decline of functional beta-cells and is usually accompanied by a reduced sensitivity to insulin. Whereas altered beta-cell function plays a key role in T2D onset, a decreased beta-cell mass was also reported to contribute to the pathophysiology of this metabolic disease. The decreased beta-cell mass in T2D is, at least in part, attributed to beta-cell apoptosis that is triggered by diabetogenic situations such as amyloid deposits, lipotoxicity and glucotoxicity. In this review, we discussed the molecular mechanisms involved in pancreatic beta-cell apoptosis under such diabetes-prone situations. Finally, we considered the molecular signaling pathways recruited by glucagon-like peptide-1-based therapies to potentially protect beta-cells from death under diabetogenic situations.

Cocoa-rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis

2015 ◽  
Vol 59 (4) ◽  
pp. 820-824 ◽  
Author(s):  
Elisa Fernández-Millán ◽  
Isabel Cordero-Herrera ◽  
Sonia Ramos ◽  
Fernando Escrivá ◽  
Carmen Alvarez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Mass Loss ◽  
Cell Apoptosis ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Apoptosis ◽  
Zucker Diabetic Fatty Rats ◽  
And Function

scholarly journals The postnatal growth of the beta-cell mass in pigs

2003 ◽  
Vol 179 (2) ◽  
pp. 245-252 ◽  
Author(s):  
T Bock ◽  
A Kyhnel ◽  
B Pakkenberg ◽  
K Buschard
Keyword(s):  
Beta Cell ◽  
Linear Relationship ◽  
Body Mass ◽  
Cell Apoptosis ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Postnatal Growth ◽  
The Body ◽  
Constant Level ◽  
Beta Cell Apoptosis

Studies of the postnatal growth of the beta-cell mass in rats have revealed some unexpected and apparently paradoxical results, the most prominent being a beta-cell mass plateau in the early phase of life. We have studied the postnatal growth of the beta-cell mass in the domestic pig to investigate its development in a larger mammal. The pancreases from a total of 86 male pigs from 5 to 100 days of age were studied. The beta-cell mass increased linearly from day 5 to day 40, reached a plateau from day 40 to day 60, and then increased further into adulthood. The relative beta-cell mass (beta-cell mass per body mass) was increased in the early postnatal period but reached a constant level from day 60, after which there was a linear relationship between the beta-cell mass and the body mass. There were high rates of both beta-cell apoptosis and mitosis at 50 and 60 days of age, while the Volume-weighted mean islet Volume increased from birth and reached a plateau at approximately 60 days of age. A beta-cell mass plateau early in life accompanied by a wave of beta-cell apoptosis coinciding with the relative beta-cell mass decreasing to reach a constant level, and a linear relationship between the beta-cell mass and the body mass in later life is exactly what has previously been reported in rats. The coincidence of these events in both rats and pigs, although occurring at different ages in the two species, suggests a causal relationship as previously suggested in a proposed explanatory model for postnatal beta-cell growth.

Investigation on the Protective Effect of Canagliflozin on Pancreatic Beta-Cell Mass Using SPECT/CT Imaging with 111In-Labeled Exendin-4

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2124-P
Author(s):  
KEITA HAMAMATSU ◽  
HIROYUKI FUJIMOTO ◽  
NAOTAKA FUJITA ◽  
TAKAAKI MURAKAMI ◽  
MASAHARU SHIOTANI ◽  
...  
Keyword(s):  
Beta Cell ◽  
Protective Effect ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Ct Imaging ◽  
Pancreatic Beta Cell Mass

Novel Use of Agent11C-PHNO for Pet CT Imaging of Pancreatic Beta-Cell Mass

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2145-P
Author(s):  
ELIZABETH SANCHEZ RANGEL ◽  
JASON BINI ◽  
NABEEL B. NABULSI ◽  
YIYUN HUANG ◽  
KEVAN C. HEROLD ◽  
...  
Keyword(s):  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Ct Imaging ◽  
Pet Ct ◽  
Pancreatic Beta Cell Mass
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