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

Costes, Safia; Bertrand, Gyslaine; Ravier, Magalie A.

doi:10.3390/ijms22105303

Cited by 37 publications

(33 citation statements)

References 224 publications

(366 reference statements)

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“…A low innate beta-cell mass, a failed increase in betacell mass in response to insulin resistance 3 or senescence, 6 and/or a progressive beta-cell loss caused by apoptosis, 3 ferroptosis 7 or dedifferentiation 8 have been highlighted to explain the default in beta-cell mass associated with T2DM. 9 Studies on the isolated human islets of subjects with T2DM show that beta-cell apoptosis plays a major in the pathogenesis of T2DM. 10,11 Type 1 diabetes (T1DM) depends on autoimmune destruction of the pancreatic beta-cells.…”

Section: Introductionmentioning

confidence: 99%

Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract

Portincasa

Bonfrate

Wang

et al. 2022

Eur J Clin Investigation

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Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.

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Section: Introductionmentioning

confidence: 99%

Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract

Portincasa

Bonfrate

Wang

et al. 2022

Eur J Clin Investigation

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“…ER stress plays a causative role in beta-cell dysfunction in overexpressing hIAPP [ 54 ]. hAIPP transgenic and non-transgenic mouse islets induce oxidative stress, and amyloid formation mediates β-cell apoptosis [ 55 , 56 ]. In the present study, ER stress and oxidative stress influenced the CHOP protein levels in hIAPP-overexpressing cells with the change of Bcl-2 and Bax protein levels.…”

Section: Discussionmentioning

confidence: 99%

Human Islet Amyloid Polypeptide Overexpression in INS-1E Cells Influences Amylin Oligomerization under ER Stress and Oxidative Stress

Yoo

Joo

2021

IJMS

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Human amylin or islet amyloid polypeptide (hIAPP) is synthesized in the pancreatic β-cells and has been shown to contribute to the pathogenesis of type 2 diabetes (T2D) in vitro and in vivo. This study compared amylin oligomerization/expression and signal transduction under endoplasmic reticulum (ER) stress and oxidative stress. pCMV-hIAPP-overexpressing INS-1E cells presented different patterns of amylin oligomerization/expression under ER stress and oxidative stress. Amylin oligomerization/expression under ER stress showed three amylin oligomers of less than 15 kDa size in pCMV-hIAPP-overexpressing cells, while one band was detected under oxidative stress. Under ER stress conditions, HIF1α, p-ERK, CHOP, Cu/Zn-SOD, and Bax were significantly increased in pCMV-hIAPP-overexpressing cells compared to the pCMV-Entry-expressing cells (control), whereas p-Akt, p-mTOR, Mn-SOD, catalase, and Bcl-2 were significantly decreased. Under oxidative stress conditions, HIF1α, p-ERK, CHOP, Mn-SOD, catalase, and Bcl-2 were significantly reduced in pCMV-hIAPP-overexpressing cells compared to the control, whereas p-mTOR, Cu/Zn-SOD, and Bax were significantly increased. In mitochondrial oxidative phosphorylation (OXPHOS), the mitochondrial complex I and complex IV were significantly decreased under ER stress conditions and significantly increased under oxidative stress conditions in pCMV-hIAPP-overexpressing cells compared to the control. The present study results demonstrate that amylin undergoes oligomerization under ER stress in pCMV-hIAPP-overexpressing cells. In addition, human amylin overexpression under ER stress in the pancreatic β cells may enhance amylin protein aggregation, resulting in β-cell dysfunction.

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“…A decrease in the number of β-cells, which produce and secrete insulin, contributes to the pathophysiology of DM [ 69 ]. The death of and dysfunctions in β-cells have been implicated in the development of glucotoxicity, lipotoxicity, and oxidative stress [ 70 , 71 ]. Autophagy protects β-cells against dysfunction and death in DM [ 70 ].…”

Section: Cytotoxicity Of Tagementioning

confidence: 99%

Effects of Toxic AGEs (TAGE) on Human Health

Takeuchi

Sakasai-Sakai

Takata

et al. 2022

Cells

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The habitual and excessive consumption of sugar (i.e., sucrose and high-fructose corn syrup, HFCS) is associated with the onset and progression of lifestyle-related diseases (LSRD). Advanced glycation end-products (AGEs) have recently been the focus of research on the factors contributing to LSRD. Approaches that inhibit the effects of AGEs may be used to prevent and/or treat LSRD; however, since the structures of AGEs vary depending on the type of reducing sugars or carbonyl compounds to which they respond, difficulties are associated with verifying that AGEs are an etiological factor. Cytotoxic AGEs derived from glyceraldehyde, a triose intermediate in the metabolism of glucose and fructose, have been implicated in LSRD and are called toxic AGEs (TAGE). A dietary imbalance (the habitual and excessive intake of sucrose, HFCS, or dietary AGEs) promotes the generation/accumulation of TAGE in vivo. Elevated circulating levels of TAGE have been detected in non-diabetics and diabetics, indicating a strong relationship between the generation/accumulation of TAGE in vivo and the onset and progression of LSRD. We herein outline current findings on “TAGE as a new target” for human health.

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

Cited by 37 publications

References 224 publications

Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract

Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract

Human Islet Amyloid Polypeptide Overexpression in INS-1E Cells Influences Amylin Oligomerization under ER Stress and Oxidative Stress

Effects of Toxic AGEs (TAGE) on Human Health

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