Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes

Wang, Zhongying; Gurlo, Tatyana; Matveyenko, Aleksey V.; Elashoff, David; Wang, Peiyu; Rosenberger, Madeline; Junge, Jason A.; Stevens, Raymond C.; White, Kate L.; Fraser, Scott E.; Butler, Peter C.

doi:10.1038/s42003-021-02113-1

Cited by 29 publications

(29 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the metabolic shift towards oxidative phosphorylation after glucose stimulation observed in β-like cells was recently confirmed in the work by Wang and collaborators [ 29 ]. Here, the single-cell resolution typical of the phasor-FLIM approach was exploited to distinguish the metabolic signature of β- and α-cells in intact murine islets ( Figure 5 ) [ 29 ]. The authors, based on obtained results, suggest that in healthy cells glucose enhances oxidative phosphorylation in β-cells and suppresses oxidative phosphorylation in α-cells.…”

Section: Optical Microscopy To Study Glucose Metabolism In β-Cellsmentioning

confidence: 58%

β-Cell Pathophysiology: A Review of Advanced Optical Microscopy Applications

Ferri

Pesce

Tesi

et al. 2021

IJMS

View full text Add to dashboard Cite

β-cells convert glucose (input) resulting in the controlled release of insulin (output), which in turn has the role to maintain glucose homeostasis. β-cell function is regulated by a complex interplay between the metabolic processing of the input, its transformation into second-messenger signals, and final mobilization of insulin-containing granules towards secretion of the output. Failure at any level in this process marks β-cell dysfunction in diabetes, thus making β-cells obvious potential targets for therapeutic purposes. Addressing quantitatively β-cell (dys)function at the molecular level in living samples requires probing simultaneously the spatial and temporal dimensions at the proper resolution. To this aim, an increasing amount of research efforts are exploiting the potentiality of biophysical techniques. In particular, using excitation light in the visible/infrared range, a number of optical-microscopy-based approaches have been tailored to the study of β-cell-(dys)function at the molecular level, either in label-free mode (i.e., exploiting intrinsic autofluorescence of cells) or by the use of organic/genetically-encoded fluorescent probes. Here, relevant examples from the literature are reviewed and discussed. Based on this, new potential lines of development in the field are drawn.

show abstract

Section: Optical Microscopy To Study Glucose Metabolism In β-Cellsmentioning

confidence: 58%

β-Cell Pathophysiology: A Review of Advanced Optical Microscopy Applications

Ferri

Pesce

Tesi

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Similar beta cell subpopulations have been described that are capable of disproportionate control of islet function, including first responder cells (222), as well as ChR2.0 cells (447), and it is likely that there is some overlap between such populations and hubs/leaders. Pertinently, FLIM imaging supports the existence of hub-like cells that metabolically recruite other cells into oxidative phosphorylation (442).…”

Section: Syncytial Beta Cell Functionmentioning

confidence: 81%

Cell Networks in Endocrine/Neuroendocrine Gland Function

Guérineau

Campos

Tissier

et al. 2022

Comprehensive Physiology

View full text Add to dashboard Cite

Reproduction, growth, stress and metabolism are determined by endocrine/neuroendocrine systems that regulate circulating hormone concentrations. All these systems generate rhythms and changes in hormone pulsatility observed in a variety of pathophysiological states. Thus, the output of endocrine/neuroendocrine systems must be regulated within a narrow window of effective hormone concentrations but must also maintain a capacity for plasticity to respond to changing physiological demands. Remarkably most endocrinologists still have a 'textbook' view of endocrine gland organization which has emanated from 20 th century histological studies on thin 2D tissue sections. However, 21 st century technological advances, including indepth 3D imaging of specific cell types have vastly changed our knowledge. We now know that various levels of multi-cellular organization can be found across different glands, that organizational motifs can vary between species and can be modified to enhance or decrease hormonal release. This review focuses on how the organization of cells regulates hormone output using three endocrine/neuroendocrine glands that present different levels of organization and complexity: the adrenal medulla, with a single neuroendocrine cell type; the anterior pituitary, with multiple intermingled cell types; and the pancreas with multiple intermingled cell types organized into distinct functional units. We give an overview of recent methodologies that allow the study of the different components within endocrine systems, and particularly their temporal and spatial relationships. We believe the emerging findings about network organization, and its impact on hormone secretion, are crucial to understanding how homeostatic regulation of endocrine axes is carried out within endocrine organs themselves.

show abstract

“…This assumption is supported by the accumulation of unfolded protein masses and amyloids that are known to be diabetogenic factors responsible for both the induction of apoptosis and the progressive functional incompetence of beta-cells [ 158 ]. In addition, in beta-cells undergoing ER stress and accumulating toxic oligomers of the unfolded protein, glucose metabolism is remodeled under conditions of hyperglycemia [ 159 ]. It is noteworthy that glutathione has also been shown to prevent beta-cell dedifferentiation and failure caused by chronic oscillating glucose intake [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Glutathione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression

Azarova

Klyosova

Полоников

2021

Life

View full text Add to dashboard Cite

The present study investigated whether type 2 diabetes (T2D) is associated with polymorphisms of genes encoding glutathione-metabolizing enzymes such as glutathione synthetase (GSS) and gamma-glutamyl transferase 7 (GGT7). A total of 3198 unrelated Russian subjects including 1572 T2D patients and 1626 healthy subjects were enrolled. Single nucleotide polymorphisms (SNPs) of the GSS and GGT7 genes were genotyped using the MassArray-4 system. We found that the GSS and GGT7 gene polymorphisms alone and in combinations are associated with T2D risk regardless of sex, age, and body mass index, as well as correlated with plasma glutathione, hydrogen peroxide, and fasting blood glucose levels. Polymorphisms of GSS (rs13041792) and GGT7 (rs6119534 and rs11546155) genes were associated with the tissue-specific expression of genes involved in unfolded protein response and the regulation of proteostasis. Transcriptome-wide association analysis has shown that the pancreatic expression of some of these genes such as EDEM2, MYH7B, MAP1LC3A, and CPNE1 is linked to the genetic risk of T2D. A comprehensive analysis of the data allowed proposing a new hypothesis for the etiology of type 2 diabetes that endogenous glutathione deficiency might be a key condition responsible for the impaired folding of proinsulin which triggered an unfolded protein response, ultimately leading to beta-cell apoptosis and disease development.

show abstract

Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes

Cited by 29 publications

References 43 publications

β-Cell Pathophysiology: A Review of Advanced Optical Microscopy Applications

β-Cell Pathophysiology: A Review of Advanced Optical Microscopy Applications

Cell Networks in Endocrine/Neuroendocrine Gland Function

The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Glutathione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression

Contact Info

Product

Resources

About