scholarly journals Epigallocatechin gallate delays the onset of type 1 diabetes in spontaneous non-obese diabetic mice

2010 ◽  
Vol 105 (8) ◽  
pp. 1218-1225 ◽  
Author(s):  
Zhuo Fu ◽  
Wei Zhen ◽  
Julia Yuskavage ◽  
Dongmin Liu
Keyword(s):  
Type 1 Diabetes ◽  
Cell Mass ◽  
Epigallocatechin Gallate ◽  
Nod Mice ◽  
Cost Effective ◽  
Treated Group ◽  
Control Group ◽  
Plasma Insulin Levels ◽  
Glucose Lowering Effect

Type 1 diabetes (T1D) results from the autoimmune-mediated destruction of pancreatic β-cells, leading to deficiency of insulin production. Successful islet transplantation can normalise hyperglycaemia in T1D patients; however, the limited availability of the islets, loss of islet cell mass through apoptosis after islet isolation and potential autoimmune destruction of the transplanted islets prevent the widespread use of this procedure. Therefore, the search for novel and cost-effective agents that can prevent or treat T1D is extremely important to decrease the burden of morbidity from this disease. In the present study, we discovered that ( − )-epigallocatechin gallate (EGCG, 0·05 % in drinking-water), the primary polyphenolic component in green tea, effectively delayed the onset of T1D in non-obese diabetic (NOD) mice. At 32 weeks of age, eight (66·7 %) out of twelve mice in the control group developed diabetes, whereas only three (25 %) out of twelve mice in the EGCG-treated group became diabetic (P < 0·05). Consistently, mice supplemented with EGCG had significantly higher plasma insulin levels and survival rate but lower glycosylated Hb concentrations compared with the control animals. EGCG had no significant effects on food or water intake and body weight in mice, suggesting that the glucose-lowering effect was not due to an alteration in these parameters. While EGCG did not modulate insulitis, it elevated the circulating anti-inflammatory cytokine IL-10 level in NOD mice. These findings demonstrate that EGCG may be a novel, plant-derived compound capable of reducing the risk of T1D.

scholarly journals One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Lu ◽  
Shan-mei Shen ◽  
Qing Ling ◽  
Bin Wang ◽  
Li-rong Li ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Stromal Cells ◽  
Treated Group ◽  
Control Group ◽  
Adult Onset ◽  
Β Cell ◽  
Juvenile Onset ◽  
C Peptide

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

scholarly journals Detecting Insulitis in Type 1 Diabetes with Ultrasound Phase-change Contrast Agents

2020 ◽  
Author(s):  
David G. Ramirez ◽  
Awaneesh K. Upadhyay ◽  
Vinh T. Pham ◽  
Mark Ciccaglione ◽  
Mark A Borden ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Contrast Agents ◽  
Cell Mass ◽  
Nod Mice ◽  
Therapeutic Interventions ◽  
Β Cells ◽  
Β Cell ◽  
Diabetes Onset ◽  
Ultrasound Contrast

AbstractType 1 diabetes (T1D) results from immune infiltration and destruction of insulin-producing β-cells within the pancreatic islets of Langerhans (insulitis), resulting in loss of glucose homeostasis. Early diagnosis during pre-symptomatic T1D would allow for therapeutic intervention prior to substantial loss of β-cell mass at T1D onset. There are limited methods to track the progression of insulitis and β-cell mass decline in pre-symptomatic T1D. During insulitis, the islet microvasculature increases permeability, such that sub-micron sized particles can extravasate and accumulate within the islet microenvironment. Ultrasound is a widely deployable and cost-effective clinical imaging modality. However, conventional microbubble contrast agents are restricted to the vasculature. Sub-micron sized nanodroplet (ND) phasechange agents can be vaporized into micron-sized bubbles; serving as a circulating microbubble precursor. We tested if NDs extravasate into the immune-infiltrated islet microenvironment. We performed ultrasound contrast-imaging following ND infusion in NOD mice and NOD;Rag1ko controls, and tracked diabetes development. We measured the biodistribution of fluorescently labeled NDs, with histological analysis of insulitis. Ultrasound contrast signal was elevated in the pancreas of 10w NOD mice following ND infusion and vaporization, but was absent in both the non-infiltrated kidney of NOD mice and pancreas of Rag1ko controls. High contrast elevation also correlated with rapid diabetes onset. In pancreata of NOD mice, infiltrated islets and nearby exocrine tissue were selectively labeled with fluorescent NDs. Thus, contrast ultrasound imaging with ND phase-change agents can detect insulitis prior to diabetes onset. This will be important for monitoring disease progression to guide and assess preventative therapeutic interventions for T1D.SignificanceThere is a need for imaging methods to detect type1 diabetes (T1D) progression prior to clinical diagnosis. T1D is a chronic disease that results from autoreactive T cells infiltrating the islet of Langerhans and destroying insulin-producing β-cells. Overt disease takes years to present and is only diagnosed after significant β-cells loss. As such, the possibility of therapeutic intervention to preserve β-cell mass is hampered by an inability to follow pre-symptomatic T1D progression. There are immunotherapies that can delay T1D development. However identifying ‘at risk’ individuals, and tracking whether therapeutic interventions are impacting disease progression, prior to T1D onset, is lacking. A method to detect insulitis and β-cell mass decline would present an opportunity to guide therapeutic treatments to prevent T1D.

scholarly journals Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes

2018 ◽  
Vol 103 (5) ◽  
pp. 1966-1976 ◽  
Author(s):  
Arianne Aslamy ◽  
Eunjin Oh ◽  
Miwon Ahn ◽  
Abu Saleh Md Moin ◽  
Mariann Chang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Cell Mass ◽  
Nod Mice ◽  
Human Islets ◽  
Β Cell ◽  
New Onset

Abstract Context Efforts to preserve β-cell mass in the preclinical stages of type 1 diabetes (T1D) are limited by few blood-derived biomarkers of β-cell destruction. Objective Platelets are proposed sources of blood-derived biomarkers for a variety of diseases, and they show distinct proteomic changes in T1D. Thus, we investigated changes in the exocytosis protein, double C2 domain protein-β (DOC2B) in platelets and islets from T1D humans, and prediabetic nonobese diabetic (NOD) mice. Design, Patients, and Main Outcome Measure Protein levels of DOC2B were assessed in platelets and islets from prediabetic NOD mice and humans, with and without T1D. Seventeen new-onset T1D human subjects (10.3 ± 3.8 years) were recruited immediately following diagnosis, and platelet DOC2B levels were compared with 14 matched nondiabetic subjects (11.4 ± 2.9 years). Furthermore, DOC2B levels were assessed in T1D human pancreatic tissue samples, cytokine-stimulated human islets ex vivo, and platelets from T1D subjects before and after islet transplantation. Results DOC2B protein abundance was substantially reduced in prediabetic NOD mouse platelets, and these changes were mirrored in the pancreatic islets from the same mice. Likewise, human DOC2B levels were reduced over twofold in platelets from new-onset T1D human subjects, and this reduction was mirrored in T1D human islets. Cytokine stimulation of normal islets reduced DOC2B expression ex vivo. Remarkably, platelet DOC2B levels increased after islet transplantation in patients with T1D. Conclusions Reduction of DOC2B is an early feature of T1D, and DOC2B abundance may serve as a valuable in vivo indicator of β-cell mass and an early biomarker of T1D.

scholarly journals Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis and β-cell mass decline in mouse models of type 1 diabetes

2019 ◽  
Author(s):  
David G. Ramirez ◽  
Eric Abenojar ◽  
Christopher Hernandez ◽  
Lucine A. Papazian ◽  
Samantha Passman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mouse Models ◽  
Cell Mass ◽  
Nod Mice ◽  
Contrast Enhanced Ultrasound ◽  
Β Cell ◽  
Ultrasound Contrast ◽  
Contrast Enhanced ◽  
Asymptomatic Phase

ABSTRACTType 1 diabetes (T1D) is characterized by the infiltration of autoreactive T-cells into the islet of Langerhans, and depletion of insulin-secreting β-cells. This immune cell infiltration (insulitis) first occurs during an asymptomatic phase of T1D that can take place many years prior to clinical diagnosis. Methods to diagnose insulitis and changes in β-cell mass during this asymptomatic phase are limited, thus precluding early therapeutic intervention. While therapeutic treatments can delay T1D progression, treatment efficacy is limited and widely varying, and a method to track this efficacy is also lacking. During T1D progression, the islet microvasculature increases permeability as a result of insulitis, in both mouse models of T1D and humans with T1D. This increased permeability can allow nanoparticles, such as contrast agents for diagnostic imaging, to access the islet microenvironment. Contrast enhanced ultrasound (CEUS) uses shell-stabilized gas bubbles to provide high acoustic backscatter in vasculature and tissue and is clinically approved. A novel, sub-micron sized ‘nanobubble’ (NB) ultrasound contrast agent has been developed and shown to extravasate and accumulate in tumors, where microvascular permeability is high. To test whether CEUS can be used to measure increased islet microvasculature permeability and indicate the asymptomatic phase of T1D, we applied CEUS measurements with NBs in pre-clinical T1D models. NOD mice and mice receiving an adoptive-transfer of diabetogenic splenocytes showed accumulation of NBs specifically within the pancreatic islets, and only in the presence of insulitis. This accumulation was measured by both ultrasound contrast and histological analysis, and accumulation only occurred for sub-micron sized bubbles. Importantly, accumulation was detected as early as 4w in NOD mice. Thus, CEUS with sub-micron sized NB contrast agent may provide a predicative marker for disease progression early in asymptomatic T1D, as well as monitoring of disease prevention or reversal.

scholarly journals Streptozotocin-Induced Diabetes in a Mouse Model (BALB/c) Is Not an Effective Model for Research on Transplantation Procedures in the Treatment of Type 1 Diabetes

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1790
Author(s):  
Michal Wszola ◽  
Marta Klak ◽  
Anna Kosowska ◽  
Grzegorz Tymicki ◽  
Andrzej Berman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mouse Model ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Control Group ◽  
Diabetes In Animals ◽  
C Peptide ◽  
Diabetes Model

Type 1 diabetes (T1D) is characterized by the destruction of over 90% of the β-cells. C-peptide is a parameter for evaluating T1D. Streptozotocin (STZ) is a standard method of inducing diabetes in animals. Eight protocols describe the administration of STZ in mice; C-peptide levels are not taken into account. The aim of the study is to determine whether the STZ protocol for the induction of beta-cell mass destruction allows for the development of a stable in vivo mouse model for research into new transplant procedures in the treatment of type 1 diabetes. Materials and methods: Forty BALB/c mice were used. The animals were divided into nine groups according to the STZ dose and a control group. The STZ doses were between 140 and 400 mg/kg of body weight. C-peptide was taken before and 2, 7, 9, 12, 14, and 21 days after STZ. Immunohistochemistry was performed. The area of the islet and insulin-/glucagon-expressing tissues was calculated. Results: Mice who received 140, 160, 2 × 100, 200, and 250 mg of STZ did not show changes in mean fasting C-peptide in comparison to the control group and to day 0. All animals with doses of 300 and 400 mg of STZ died during the experiment. The area of the islets did not show any differences between the control and STZ-treated mice in groups below 300 mg. The reduction of insulin-positive areas in STZ mice did not exceed 50%. Conclusions: Streptozotocin is not an appropriate method of inducing a diabetes model for further research on transplantation treatments of type 1 diabetes, having caused the destruction of more than 90% of the β-cell mass in BALB/c mice.

Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse

2013 ◽  
Vol 126 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Abhirup Jayasimhan ◽  
Kristy P. Mansour ◽  
Robyn M. Slattery
Keyword(s):  
Type 1 Diabetes ◽  
Cell Mass ◽  
Nod Mice ◽  
Diabetic Mouse ◽  
Nod Mouse ◽  
Β Cells ◽  
Autoimmune Destruction ◽  
Immune Mediated ◽  
And Function

T1D (Type 1 diabetes) is an autoimmune disease caused by the immune-mediated destruction of pancreatic β-cells. Studies in T1D patients have been limited by the availability of pancreatic samples, a protracted pre-diabetic phase and limitations in markers that reflect β-cell mass and function. The NOD (non-obese diabetic) mouse is currently the best available animal model of T1D, since it develops disease spontaneously and shares many genetic and immunopathogenic features with human T1D. Consequently, the NOD mouse has been extensively studied and has made a tremendous contribution to our understanding of human T1D. The present review summarizes the key lessons from NOD mouse studies concerning the genetic susceptibility, aetiology and immunopathogenic mechanisms that contribute to autoimmune destruction of β-cells. Finally, we summarize the potential and limitations of immunotherapeutic strategies, successful in NOD mice, now being trialled in T1D patients and individuals at risk of developing T1D.

1190-P: IFN-Alpha Kinoid: A Promising Vaccine against Type 1 Diabetes Targeting IFN-alpha in NOD Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1190-P
Author(s):  
NOÉMIE CAILLOT ◽  
FABIEN COLAONE ◽  
ROMAIN BERTRAND ◽  
JENNIFER DA SILVA ◽  
SAMIR HAMDI ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice ◽  
Ifn Alpha

PBI-4547 Prevents Progression of Prediabetic Condition to Type 1 Diabetes in NOD Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1817-P
Author(s):  
FRANÇOIS A. LEBLOND ◽  
KATHY HINCE ◽  
FRANÇOIS SARRA-BOURNET ◽  
WILLIAM GAGNON ◽  
MIKAËL TREMBLAY ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice

Features of the ovarian reserve of women of reproductive age suffering from autoimmune diseases

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. 27-30
Author(s):  
Elena N. Andreeva ◽  
Olga R. Grigoryan ◽  
Yulia S. Absatarova ◽  
Irina S. Yarovaya ◽  
Robert K. Mikheev
Keyword(s):  
Type 1 Diabetes ◽  
Thyroid Gland ◽  
Autoimmune Diseases ◽  
Ovarian Reserve ◽  
Reproductive Potential ◽  
Reproductive Age ◽  
Control Group ◽  
Antithyroid Antibodies ◽  
Healthy Women

The reproductive potential of a woman depends on indicators of the ovarian reserve, such as the anti-Muller hormone (AMH) and the number of antral follicles (NAF). Autoimmune diseases have a significant effect on fertility and contribute to the development of premature ovarian failure. Aim.To evaluate the parameters of the ovarian reserve in patients with type 1 diabetes mellitus, carriers of antibodies to the thyroid gland in a state of euthyroidism and compare them with similar parameters in healthy women. Materials and methods.In the first block of the study, the level of AMH, follicle-stimulating hormone, luteinizing hormone, NAF was studied among 224 women with diabetes and 230 healthy women in the control group. In block II, the level of the above hormonal indices was studied in 35 carriers of antithyroid antibodies in the state of euthyroidism and 35 healthy women. Results.In patients with type 1 diabetes, the level of AMH, NAF was statistically significantly lower when compared with the control group. Among carriers of antithyroid antibodies and healthy women, no difference in AMH and NAF was found. Conclusion.The autoimmune processes accompanying diabetes are more influenced by the ovarian reserve indices than autoimmune aggression to the tissues of the thyroid gland.

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