Dataset Information

Targeting pancreatic beta cell death in type 2 diabetes by polyphenols.

ABSTRACT: Diabetes is a very complex disease which is characterized by the appearance of insulin resistance that is primarily compensated by an increase in pancreatic beta cell mass, generating hyperinsulinemia. After time, pancreatic beta cells die by apoptosis appearing in the second phase of the disease, and characterized by hypoinsulinemia. There are multiple conditions that can alter pancreatic beta cell homeostasis and viability, being the most relevant ones; ER stress, cytotoxicity by amylin, mTORC1 hyperactivity, oxidative stress, mitochondrial dysfunction, inflammation and alterations in autophagy/mitophagy flux. In addition, the possible effects that different polyphenols could exert in the modulation of these mechanisms and regulating pancreatic beta cell viability are analyzed. It is necessary a profound analysis and understanding of all the possible mechanisms involved in the control and maintenance of pancreatic beta cell viability to develop more accurate and target treatments for controlling beta cell homeostasis and preventing or even reversing type 2 diabetes mellitus.

SUBMITTER: Garcia-Aguilar A

PROVIDER: S-EPMC9712222 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeting pancreatic beta cell death in type 2 diabetes by polyphenols.

García-Aguilar Ana A Guillén Carlos C

Frontiers in endocrinology 20221117

Diabetes is a very complex disease which is characterized by the appearance of insulin resistance that is primarily compensated by an increase in pancreatic beta cell mass, generating hyperinsulinemia. After time, pancreatic beta cells die by apoptosis appearing in the second phase of the disease, and characterized by hypoinsulinemia. There are multiple conditions that can alter pancreatic beta cell homeostasis and viability, being the most relevant ones; ER stress, cytotoxicity by amylin, mTORC ...[more]

PMID: 36465657

Similar Datasets

Project description:Aims/hypothesisPancreatic beta cells are subjected to exogenous damaging factors such as proinflammatory cytokines or excess glucose that can cause accumulation of damage-inducing reactive oxygen species during the pathogenesis of diabetes. We and others have shown that beta cell autophagy can reduce reactive oxygen species to protect against apoptosis. While impaired islet autophagy has been demonstrated in human type 2 diabetes, it is unknown if islet autophagy is perturbed in the pathogenesis of type 1 diabetes. We hypothesised that beta cell autophagy is dysfunctional in type 1 diabetes, and that there is a progressive loss during early diabetes development.MethodsPancreases were collected from chloroquine-injected and non-injected non-obese diabetes-resistant (NOR) and non-obese diabetic (NOD) mice. Age- and BMI-matched pancreas tissue sections from human organ donors (N = 34) were obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD). Tissue sections were stained with antibodies against proinsulin or insulin (beta cell markers), microtubule-associated protein 1 light chain 3 A/B (LC3A/B; autophagosome marker), lysosomal-associated membrane protein 1 (LAMP1; lysosome marker) and p62 (autophagy adaptor). Images collected on a scanning laser confocal microscope were analysed with CellProfiler and ImageJ. Secondary lysosomes and telolysosomes were assessed in electron micrographs of human pancreatic tissue sections (n = 12), and energy dispersive x-ray analysis was performed to assess distribution of elements (n = 5).ResultsWe observed increased autophagosome numbers in islets of diabetic NOD mice (p = 0.008) and increased p62 in islets of both non-diabetic and diabetic NOD mice (p < 0.001) vs NOR mice. There was also a reduction in LC3-LAMP1 colocalisation in islets of diabetic NOD mice compared with both non-diabetic NOD (p < 0.001) and NOR mice (p < 0.001). Chloroquine elicited accumulation of autophagosomes in the islets of NOR (p = 0.003) and non-diabetic NOD mice (p < 0.001), but not in islets of diabetic NOD mice; and stimulated accumulation of p62 in NOR (p < 0.001), but not in NOD mice. We observed reduced LC3-LAMP1 colocalisation (p < 0.001) in residual beta cells of human donors with type 1 diabetes vs non-diabetic participants. We also observed reduced colocalisation of proinsulin with LAMP1 in donors with type 1 diabetes (p < 0.001). Electron microscopy also revealed accumulation of telolysosomes with nitrogen-dense rings in beta cells of autoantibody-positive donors (p = 0.002).Conclusions/interpretationWe provide evidence of islet macroautophagy/crinophagy impairment in human type 1 diabetes. We also document accumulation of telolysosomes with peripheral nitrogen in beta cells of autoantibody-positive donors, demonstrating altered lysosome content that may be associated with lysosome dysfunction before clinical hyperglycaemia. Similar macroautophagy impairments are present in the NOD mouse model of type 1 diabetes.

Dataset Information

Targeting pancreatic beta cell death in type 2 diabetes by polyphenols.

Publications

Targeting pancreatic beta cell death in type 2 diabetes by polyphenols.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets