Dataset Information

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.

ABSTRACT:

Aims/hypothesis

In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells during chronic glucose stress.

Methods

Respiration and cytosolic ATP changes were measured in human islet cell clusters after culture for 4 days in 11.1 mmol/l glucose. Metabolomics was applied to analyse intracellular metabolite changes as a result of glucose stress conditions. Alterations in beta cell function were followed using insulin secretion assays or cytosolic calcium signalling after expression of the calcium probe YC3.6 specifically in beta cells of islet clusters.

Results

At early stages of glucose stress, mitochondrial energy metabolism was augmented in contrast to the previously described mitochondrial dysfunction in beta cells from islets of diabetic donors. Following chronic glucose stress, mitochondrial respiration increased (by 52.4%, p?Conclusion/interpretationWe propose that metabolic changes and associated mitochondrial overactivation are early adaptations to glucose stress, and may reflect what happens as a result of poor blood glucose control. Inhibition of mitochondrial pyruvate transport reduces mitochondrial nutrient overload and allows beta cells to recover from chronic glucose stress. Graphical abstract.

SUBMITTER: Chareyron I

PROVIDER: S-EPMC7641954 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.

Chareyron Isabelle I Christen Stefan S Moco Sofia S Valsesia Armand A Lassueur Steve S Dayon Loïc L Wollheim Claes B CB Santo Domingo Jaime J Wiederkehr Andreas A

Diabetologia 20200922 12

<h4>Aims/hypothesis</h4>In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells during chronic glucose stress.<h4>Methods</h4>Respiration and cytosolic ATP changes were measured in human islet cell clusters after culture for 4 days in 11.1 mmol/l glucose. Metabolomics was applied to analyse intracellular metabolite chan ...[more]

PMID: 32960311

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Dataset Information

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.

Aims/hypothesis

Methods

Results

Publications

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.

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