Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting regulatory T cells in the treatment of type 1 diabetes mellitus.

ABSTRACT: Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease resulting in islet ? cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. T1DM has classically been attributed to the pathogenic actions of auto-reactive effector T cells(Teffs) on the ? cell. Recent literature now suggests that a failure of a second T cell subtype, known as regulatory T cells (Tregs), plays a critical role in the development of T1DM. During immune homeostasis, Tregs counterbalance the actions of autoreactive Teff cells, thereby participating in peripheral tolerance. An imbalance in the activity between Teff and Tregs may be crucial in the breakdown of peripheral tolerance, leading to the development of T1DM. In this review, we summarize our current understanding of Treg function in health and in T1DM, and examine the effect of experimental therapies for T1DM on Treg cell number and function in both mice and humans.

SUBMITTER: Cabrera SM

PROVIDER: S-EPMC3709459 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Targeting regulatory T cells in the treatment of type 1 diabetes mellitus.

Cabrera S M SM Rigby M R MR Mirmira R G RG

Current molecular medicine 20121201 10

Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease resulting in islet β cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. T1DM has classically been attributed to the pathogenic actions of auto-reactive effector T cells(Teffs) on the β cell. Recent literature now suggests that a failure of a second T cell subtype, known as regulatory T cells (Tregs), plays a critical role in the development of T1DM. During immune homeostasis, Tregs counterbalance th ...[more]

PMID: 22709273

Similar Datasets

SGLT2 Inhibitors for Type 2 Diabetes Mellitus Treatment.

Project description:SGLT2 inhibitors are plausible second-line drugs that provide powerful additional A1c-lowering effects while inducing weight loss without hypoglycemia.

| S-EPMC6375399 | biostudies-literature

Update on the treatment of type 2 diabetes mellitus.

Project description:To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus (T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2DM, with an emphasis on agents introduced within the last decade.

| S-EPMC5027002 | biostudies-other

Treatment of type 2 diabetes mellitus in the elderly.

Project description:The prevalence of type 2 diabetes is expected to increase gradually with the prolongation of population aging and life expectancy. In addition to macrovascular and microvascular complications of elderly patients of diabetes mellitus, geriatric syndromes such as cognitive impairment, depression, urinary incontinence, falling and polypharmacy are also accompanied by aging. Individual functional status in the elderly shows heterogeneity so that in these patients, there are many unanswered questions about the management of diabetes treatment. The goals of diabetes treatment in elderly patients include hyperglycemia and risk factors, as in younger patients. comorbid diseases and functional limitations of individuals should be taken into consideration when setting treatment targets. Thus, treatment should be individualized. In the treatment of diabetes in vulnerable elderly patients, hypoglycemia, hypotension, and drug interactions due to multiple drug use should be avoided. Since it also affects the ability to self-care in these patients, management of other concurrent medical conditions is also important.

| S-EPMC5483426 | biostudies-other

Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.

Project description:Insulin-degrading enzyme (IDE) selectively degrades peptides, such as insulin, amylin, and amyloid β (Aβ) that form toxic aggregates, to maintain proteostasis. IDE defects are linked to the development of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Structural and biochemical analyses revealed the molecular basis for IDE-mediated destruction of amyloidogenic peptides and this information has been exploited to develop promising inhibitors of IDE to improve glucose homeostasis. However, the inhibition of IDE can also lead to glucose intolerance. In this review, I focus on recent advances regarding our understanding of the structure and function of IDE and the discovery of IDE inhibitors, as well as challenges in developing IDE-based therapy for human diseases, particularly T2DM.

| S-EPMC4698235 | biostudies-literature

Diabetes Mellitus Type 1 miRnome

Project description:Diabetes Mellitus Type 1 miRnome

| PRJEB51173 | ENA

Induced regulatory T cells suppress Tc1 cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus.

Project description:Type 1 diabetes mellitus (T1D) is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic β cells. In addition to well-established pathogenic effector T cells, regulatory T cells (Tregs) have also been shown to be defective in T1D. Thus, an increasing number of therapeutic approaches are being developed to target Tregs. However, the role and mechanisms of TGF-β-induced Tregs (iTregs) in T1D remain poorly understood. Here, using a streptozotocin (STZ)-induced preclinical T1D mouse model, we found that iTregs could ameliorate the development of T1D and preserve β cell function. The preventive effect was associated with the inhibition of type 1 cytotoxic T (Tc1) cell function and rebalancing the Treg/Tc1 cell ratio in recipients. Furthermore, we showed that the underlying mechanisms were due to the TGF-β-mediated combinatorial actions of mTOR and TCF1. In addition to the preventive role, the therapeutic effects of iTregs on the established STZ-T1D and nonobese diabetic (NOD) mouse models were tested, which revealed improved β cell function. Our findings therefore provide key new insights into the basic mechanisms involved in the therapeutic role of iTregs in T1D.

| S-EPMC8027661 | biostudies-literature

Canagliflozin Treatment in Patients with Type 2 Diabetes Mellitus.

Project description:Current guidelines for treatment of type 2 diabetes mellitus (T2DM) indicate a patient-centered approach that should go beyond glycemic control. Of the many antihyperglycemic agents available for treatment of T2DM, sodium-glucose cotransporter 2 (SGLT2) inhibitors offer the advantages of reduced glycated hemoglobin (A1C), body weight (BW), and systolic blood pressure (SBP) and are associated with a low risk of hypoglycemia when used either as monotherapy or with other agents not typically associated with increased risk of hypoglycemia. Collaborative, multidisciplinary teams are best suited to provide care to patients with diabetes, and clinical pharmacists can enhance the care provided by these teams. This review aims to provide insight into the mode of action, pharmacology, potential drug-drug interactions, clinical benefits, and safety considerations associated with use of the SGLT2 inhibitor canagliflozin in patients with T2DM and to provide information to enhance clinical pharmacists' understanding of canagliflozin.

| S-EPMC4610726 | biostudies-literature

Ertugliflozin in the treatment of type 2 diabetes mellitus.

Project description:More than 422 million people worldwide have diabetes, with 90-95% having type 2 diabetes (T2D). Glycemic control of T2D has demonstrated reductions in microvascular complications but recent data have demonstrated improvements in macrovascular outcomes with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Ertugliflozin is the most recent SGLT2 inhibitor approved in the USA and Europe for the treatment of T2D. This narrative review aims to present and discuss the efficacy, safety, cardiovascular (CV), and renal outcomes related to the use of ertugliflozin in T2D. Ertugliflozin has been evaluated in eight clinical trials (n=5248) with a focus on glycemic control. These trials have demonstrated improvement in glycosylated hemoglobin (0.6-1%), fasting plasma glucose (30-50 mg/dL), 2-hour postprandial glucose (60-70 mg/dL), decreased body weight (2-3 kg), and lowering of blood pressure (3-5 mmHg) in patients with T2D when ertugliflozin is used as monotherapy or in addition to metformin, sitagliptin, insulin, and/or sulfonylureas. The findings from the VERTIS-CV trial (n=8246) were recently published and demonstrated that ertugliflozin use in patients with T2D and atherosclerotic CV disease is safe but did not demonstrate superiority in the lowering of major CV events compared to placebo. Other SGLT2 inhibitors, such as empagliflozin and canagliflozin, have demonstrated this benefit. The VERTIS-CV trial demonstrated that the use of ertugliflozin led to a decrease in the number of hospitalizations for heart failure and this lends further support that this benefit is a class effect of SGLT2 inhibitors.

| S-EPMC7707814 | biostudies-literature

Trends of nanotechnology in type 2 diabetes mellitus treatment.

Project description:There are several therapeutic approaches in type 2 diabetes mellitus (T2DM). When diet and exercise fail to control hyperglycemia, patients are forced to start therapy with antidiabetic agents. However, these drugs present several drawbacks that can affect the course of treatment. The major disadvantages of current oral modalities for the treatment of T2DM are mainly depicted in the low bioavailability and the immediate release of the drug, generating the need for an increase in frequency of dosing. In conjugation with the manifestation of adverse side effects, patient compliance to therapy is reduced. Over the past few years nanotechnology has found fertile ground in the development of novel delivery modalities that can potentially enhance anti-diabetic regimes efficacy. All efforts have been targeted towards two main vital steps: (a) to protect the drug by encapsulating it into a nano-carrier system and (b) efficiently release the drug in a gradual as well as controllable manner. However, only a limited number of studies published in the literature used in vivo techniques in order to support findings. Here we discuss the current disadvantages of modern T2DM marketed drugs, and the nanotechnology advances supported by in vivo in mouse/rat models of glucose homeostasis. The generation of drug nanocarriers may increase bioavailability, prolong release and therefore reduce dosing and thus, improve patient compliance. This novel approach might substantially improve quality of life for diabetics. Application of metal nanoformulations as indirect hypoglycemic agents is also discussed.

| S-EPMC7878460 | biostudies-literature

Semaglutide for the Treatment of Type 2 Diabetes Mellitus.

Project description:Objective: To detail studies investigating the efficacy/safety of semaglutide as a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in the treatment of type 2 diabetes mellitus. Data Sources: A literature search in MEDLINE and ClinicalTrials.gov (January 2013 to May 2018) using the terms semaglutide, SUSTAIN, oral, and PIONEER resulted in 10 published articles and 14 ongoing/unpublished articles. Study Selection and Data Extraction: All English language phase 2 and 3 clinical trials evaluating efficacy/safety of semaglutide were included. Data Synthesis: In 9 phase 3, multicenter SUSTAIN trials, the efficacy and safety of semaglutide have been compared with placebo and other pharmacologic therapy for diabetes (PTD). In these trials, semaglutide resulted in lower hemoglobin A1c (HbA1c; approximately -1.5%) and weight reductions (approximately -4.5 kg) as comparable with dulaglutide for HbA1c lowering (approximately -1.5%). Semaglutide also has cardiovascular (CV) outcomes data that show significant reduction in risk of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke (hazard ratio = 0.74; 95% confidence interval = 0.58-0.95). A safety finding that emerged from the CV outcomes trial was an association of semaglutide treatment with an increased risk of retinopathy complications in patients with preexisting diabetic retinopathy. Phase 3 trial data assessing semaglutide oral formulation have shown similar HbA1c (approximately -1.5% for 14 mg dose) and body weight (approximately -4.1 kg for 14 mg dose) reductions as compared with placebo. Across these studies, semaglutide was generally well tolerated with the most common adverse event reported as gastrointestinal side effects as seen in all GLP-1 RAs. Conclusions: These results suggest that semaglutide may have a place in therapy as a GLP-1 RA add-on therapy with higher weight loss as compared with other GLP-1 RAs and PTD and CV benefit.

| S-EPMC6231279 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data