The identification of diabetes genes mediating β-cell loss and hyperglycemia using positional cloning

Pancreatic β-cell loss is critical in diabetes pathogenesis. Up to now, no effective treatment has become available for β-cell loss. A polyphenol recently isolated from Polysiphonia japonica, 5-Bromoprotocatechualdehyde (BPCA), is considered as a potential compound for the protection of β-cells. In this study, we examined palmitate (PA)-induced lipotoxicity in Ins-1 cells to test the protective effects of BPCA on insulin-secreting β-cells. Our results demonstrated that BPCA can protect β-cells from PA-induced lipotoxicity by reducing cellular damage, preventing reactive oxygen species (ROS) overproduction, and enhancing glucose-stimulated insulin secretion (GSIS). BPCA also improved mitochondrial morphology by preserving parkin protein expression. Moreover, BPCA exhibited a protective effect against PA-induced β-cell dysfunction in vivo in a zebrafish model. Our results provide strong evidence that BPCA could be a potential therapeutic agent for the management of diabetes.

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Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss

Nature ◽

10.1038/nature08894 ◽

2010 ◽

Vol 464 (7292) ◽

pp. 1149-1154 ◽

Cited By ~ 723

Author(s):

Fabrizio Thorel ◽

Virginie Népote ◽

Isabelle Avril ◽

Kenji Kohno ◽

Renaud Desgraz ◽

...

Keyword(s):

Cell Loss ◽

Β Cells ◽

Β Cell

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Circulating miRNA‐150‐5p is associated with immune‐mediated early β‐cell loss in a humanized mouse model

Xenotransplantation ◽

10.1111/xen.12474 ◽

2018 ◽

Vol 26 (2) ◽

pp. e12474 ◽

Cited By ~ 1

Author(s):

Regan Roat ◽

Md Munir Hossain ◽

Jenica Christopherson ◽

Colette Free ◽

Claudiane Guay ◽

...

Keyword(s):

Mouse Model ◽

Cell Loss ◽

Humanized Mouse ◽

Β Cell ◽

Humanized Mouse Model ◽

Circulating Mirna ◽

Immune Mediated

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The role of inflammation in insulitis and β-cell loss in type 1 diabetes

Nature Reviews Endocrinology ◽

10.1038/nrendo.2009.21 ◽

2009 ◽

Vol 5 (4) ◽

pp. 219-226 ◽

Cited By ~ 569

Author(s):

Décio L. Eizirik ◽

Maikel L. Colli ◽

Fernanda Ortis

Keyword(s):

Type 1 Diabetes ◽

Cell Loss ◽

Β Cell

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Dimorphic autoantigenic and protective effects of Reg2 peptide in the treatment of diabetic β‐cell loss

Diabetes Obesity and Metabolism ◽

10.1111/dom.13644 ◽

2019 ◽

Vol 21 (5) ◽

pp. 1209-1222 ◽

Cited By ~ 1

Author(s):

Luting Yu ◽

Xiang Li ◽

Zhiyuan Zhang ◽

Pei Du ◽

Jun‐Li Liu ◽

...

Keyword(s):

Cell Loss ◽

Protective Effects ◽

Β Cell

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Plasma GAD65, a Marker for Early β-Cell Loss After Intraportal Islet Cell Transplantation in Diabetic Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-1216 ◽

2015 ◽

Vol 100 (6) ◽

pp. 2314-2321 ◽

Cited By ~ 15

Author(s):

Zhidong Ling ◽

Pieter De Pauw ◽

Daniel Jacobs-Tulleneers-Thevissen ◽

Rui Mao ◽

Pieter Gillard ◽

...

Keyword(s):

Cell Transplantation ◽

Islet Cell ◽

Cell Loss ◽

Diabetic Patients ◽

Islet Cell Transplantation ◽

Β Cell

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Reduced Incidence and Delayed Onset of Diabetes in Perforin-deficient Nonobese Diabetic Mice

Journal of Experimental Medicine ◽

10.1084/jem.186.7.989 ◽

1997 ◽

Vol 186 (7) ◽

pp. 989-997 ◽

Cited By ~ 160

Author(s):

David Kägi ◽

Bernhard Odermatt ◽

Peter Seiler ◽

Rolf M. Zinkernagel ◽

Tak W. Mak ◽

...

Keyword(s):

T Cells ◽

Autoimmune Diabetes ◽

Cytotoxic T Cells ◽

Disease Onset ◽

Spontaneous Diabetes ◽

Cell Loss ◽

Β Cell ◽

Nonobese Diabetic ◽

Nonobese Diabetic Mice ◽

Deficient Mice

To investigate the role of T cell–mediated, perforin-dependent cytotoxicity in autoimmune diabetes, perforin-deficient mice were backcrossed with the nonobese diabetes mouse strain. It was found that the incidence of spontaneous diabetes over a 1 yr period was reduced from 77% in perforin +/+ control to 16% in perforin-deficient mice. Also, the disease onset was markedly delayed (median onset of 39.5 versus 19 wk) in the latter. Insulitis with infiltration of CD4+ and CD8+ T cells occurred similarly in both groups of animals. Lower incidence and delayed disease onset were also evident in perforin-deficient mice when diabetes was induced by cyclophosphamide injection. Thus, perforin-dependent cytotoxicity is a crucial effector mechanism for β cell elimination by cytotoxic T cells in autoimmune diabetes. However, in the absence of perforin chronic inflammation of the islets can lead to diabetogenic β cell loss by less efficient secondary effector mechanisms.

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Harnessing immune cells to enhance β-cell mass in type 1 diabetes

Journal of Investigative Medicine ◽

10.1136/jim-d-15-00196 ◽

2016 ◽

Vol 64 (1) ◽

pp. 14-20 ◽

Cited By ~ 2

Author(s):

Ercument Dirice ◽

Rohit N Kulkarni

Keyword(s):

Type 1 Diabetes ◽

Mononuclear Cells ◽

Islet Cells ◽

Cell Mass ◽

Cell Loss ◽

Cell Types ◽

Β Cells ◽

Β Cell ◽

Autoimmune Attack

Type 1 diabetes is characterized by early β-cell loss leading to insulin dependence in virtually all patients with the disease in order to maintain glucose homeostasis. Most studies over the past few decades have focused on limiting the autoimmune attack on the β cells. However, emerging data from patients with long-standing diabetes who continue to harbor functional insulin-producing cells in their diseased pancreas have prompted scientists to examine whether proliferation of existing β cells can be enhanced to promote better glycemic control. In support of this concept, several studies indicate that mononuclear cells that infiltrate the islets have the capacity to trigger proliferation of islet cells including β cells. These observations indicate the exciting possibility of identifying those mononuclear cell types and their soluble factors and harnessing their ability to promote β-cell growth concomitant with autoimmune therapy to prevent the onset and/or halt the progression of the disease.

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