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Kabra, U.* ; Affourtit, C.* ; Jastroch, M.

Respiratory parameters for the classification of dysfunctional insulin secretion by pancreatic islets.

Metabolites 11:405 (2021)
Publ. Version/Full Text DOI
Open Access Gold
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The development of obesity and type 2 diabetes (T2D) has been associated with impaired mitochondrial function. In pancreatic beta (β) cells, mitochondrial energy metabolism plays a central role in triggering and controlling glucose-stimulated insulin secretion (GSIS). Here, we have explored whether mitochondrial bioenergetic parameters assessed with Seahorse extracellular flux technology can quantitatively predict insulin secretion. We metabolically stressed male C57BL/6 mice by high-fat feeding (HFD) and measured the glucose sensitivity of islet respiration and insulin secretion. The diet-induced obese (DIO) mice developed hyperinsulinemia, but no pathological secretory differences were apparent between isolated DIO and chow islets. Real-time extracellular flux analysis, however, revealed a lower respiratory sensitivity to glucose in DIO islets. Correlation of insulin secretion with respiratory parameters uncovers compromised insulin secretion in DIO islets by oxidative power. Normalization to increased insulin contents during DIO improves the quantitative relation between GSIS and respiration, allowing to classify dysfunctional properties of pancreatic insulin secretion, and thereby serving as valuable biomarker for pancreatic islet glucose responsiveness and health.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Bioenergetics ; Glucose-stimulated Insulin Secretion ; Mitochondria ; Pancreatic Islets ; Respiration; Mechanisms; Glucose; Release
ISSN (print) / ISBN 2218-1989
e-ISSN 2218-1989
Journal Metabolites
Quellenangaben Volume: 11, Issue: 6, Pages: , Article Number: 405 Supplement: ,
Publisher MDPI
Publishing Place St Alban-anlage 66, Ch-4052 Basel, Switzerland
Reviewing status Peer reviewed
Grants Novo Nordisk Fonden