scholarly journals Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Sugyeong Jo ◽  
Sungsoon Fang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Type Ii Diabetes ◽  
Immune Modulation ◽  
Therapeutic Strategies ◽  
Immune Homeostasis ◽  
Type I ◽  
Type Ii ◽  
Pancreatic Β Cell ◽  
Β Cell

Increased incidence of type I and type II diabetes has been prevailed worldwide. Though the pathogenesis of molecular mechanisms remains still unclear, there are solid evidence that disturbed immune homeostasis leads to pancreatic β cell failure. Currently, autoimmunity and uncontrolled inflammatory signaling pathways have been considered the major factors in the pathogenesis of diabetes. Many components of immune system have been reported to implicate pancreatic β cell failure, including helper T cells, cytotoxic T cells, regulatory T cells and gut microbiota. Immune modulation of those components using small molecules and antibodies, and fecal microbiota transplantation are undergoing in many clinical trials for the treatment of type I and type II diabetes. In this review we will discuss the basis of molecular pathogenesis focusing on the disturbed immune homeostasis in type I and type II diabetes, leading to pancreatic β cell destruction. Finally, we will introduce current therapeutic strategies and clinical trials by modulation of immune system for the treatment of type I and type II diabetes patients.

Effect of porcine gastric inhibitory polypeptide on β-cell function in type I and type II diabetes mellitus

Metabolism ◽  
1987 ◽  
Vol 36 (7) ◽  
pp. 677-682 ◽  
Author(s):  
Thure Krarup ◽  
Nina Saurbrey ◽  
Alister J. Moody ◽  
Claus Kühl ◽  
Sten Madsbad
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Cell Function ◽  
Gastric Inhibitory Polypeptide ◽  
Type Ii Diabetes Mellitus ◽  
Type I ◽  
Type Ii ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Endoplasmic Reticulum Stress-Associated Lipid Droplet Formation and Type II Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Xuebao Zhang ◽  
Kezhong Zhang
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Insulin Signaling ◽  
Type Ii Diabetes ◽  
Proper Function ◽  
Type Ii ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Peripheral Insulin Resistance

Diabetes mellitus (DM), a metabolic disorder characterized by hyperglycemia, is caused by insufficient insulin production due to excessive loss of pancreatic β cells (type I diabetes) or impaired insulin signaling due to peripheral insulin resistance (type II diabetes). Pancreatic β cell is the only insulin-secreting cell type that has highly developed endoplasmic reticulum (ER) to cope with high demands of insulin synthesis and secretion. Therefore, ER homeostasis is crucial to the proper function of insulin signaling. Accumulating evidence suggests that deleterious ER stress and excessive intracellular lipids in nonadipose tissues, such as myocyte, cardiomyocyte, and hepatocyte, cause pancreatic β-cell dysfunction and peripheral insulin resistance, leading to type II diabetes. The excessive deposition of lipid droplets (LDs) in specialized cell types, such as adipocytes, hepatocytes, and macrophages, has been found as a hallmark in ER stress-associated metabolic diseases, including obesity, diabetes, fatty liver disease, and atherosclerosis. However, much work remains to be done in understanding the mechanism by which ER stress response regulates LD formation and the pathophysiologic role of ER stress-associated LD in metabolic disease. This paper briefly summarizes the recent advances in ER stress-associated LD formation and its involvement in type II diabetes.

scholarly journals A chimeric type II/type I interleukin-1 receptor can mediate interleukin-1 induction of gene expression in T cells

1993 ◽  
Vol 268 (14) ◽  
pp. 10490-10494
Author(s):  
A. Heguy ◽  
C.T. Baldari ◽  
S. Censini ◽  
P. Ghiara ◽  
J.L. Telford
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Interleukin 1 ◽  
Type I ◽  
Type Ii

scholarly journals 284: Graft Rejection as a Type I Immune Response Amenable to Modulation by Type II Donor T Cells via an “Infectious” Mechanism

2008 ◽  
Vol 14 (2) ◽  
pp. 105
Author(s):  
J. Mariotti ◽  
J. Foley ◽  
S. Amarnath ◽  
N. Buxhoeveden ◽  
K. Ryan ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Graft Rejection ◽  
Type I ◽  
Type Ii ◽  
Donor T Cells

Prednisolone enhances β-cell function independently of ambient glycemic levels in type II diabetes

Metabolism ◽  
1993 ◽  
Vol 42 (9) ◽  
pp. 1116-1120 ◽  
Author(s):  
J.P. Hosker ◽  
M.A. Burnett ◽  
D.R. Matthews ◽  
R.C. Turner
Keyword(s):  
Type Ii Diabetes ◽  
Cell Function ◽  
Type Ii ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II

2004 ◽  
Vol 199 (9) ◽  
pp. 1285-1291 ◽  
Author(s):  
Martin A. Kriegel ◽  
Tobias Lohmann ◽  
Christoph Gabler ◽  
Norbert Blank ◽  
Joachim R. Kalden ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Type I ◽  
Type Ii ◽  
Central Tolerance ◽  
Autoimmune Polyglandular Syndrome ◽  
Healthy Donors ◽  
Organ Specific ◽  
Autoimmune Polyglandular Syndrome Type

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4+ CD25+ regulatory T cells (Tregs) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. Tregs from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II Tregs were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.

Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells

1989 ◽  
Vol 9 (5) ◽  
pp. 2173-2180
Author(s):  
T Takadera ◽  
S Leung ◽  
A Gernone ◽  
Y Koga ◽  
Y Takihara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Human Peripheral Blood ◽  
Specific Gene ◽  
Type I ◽  
Type Ii ◽  
Carcinoma Cell Lines ◽  
Human T Cell

The human T-cell- or lymphocyte-specific gene, lck, encodes a tyrosine kinase and is a member of the src family. In this report we demonstrate that there are two classes of human lck transcripts (types I and II), containing different 5'-untranslated regions, which are expressed from two distinct promoters. No apparent sequence similarity was observed between the 5'-flanking regions of the two promoters. The expression of lck in human T-cell leukemia and carcinoma cell lines and in human peripheral blood T lymphocytes was examined by S1 nuclease and primer extension mapping and by Northern (RNA) blot analysis of total cellular RNA. The following results were obtained. (i) Two RNA start sites in the downstream promoter were used to generate type I transcripts. (ii) The major human type I start site has not been described for the mouse. (iii) At least five RNA start sites in the upstream promoter were used to generate type II transcripts. (iv) In T cells and in two colon carcinoma cell lines, type II transcripts were present in higher amounts than type I transcripts. (v) In T cells treated with phytohemagglutinin, tetradecanoylphorbol acetate, and cyclosporin A, the modulation of lck expression was associated primarily with changes in levels of type II transcripts. The above results suggest that the two human lck promoters are utilized differentially and may be regulated independently during certain physiological states.

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