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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Bioenergetics ; Glucose-stimulated Insulin Secretion ; Mitochondria ; Pancreatic Islets ; Respiration; Mechanisms; Glucose; Release
ISSN (print) / ISBN 2218-1989
e-ISSN 2218-1989
Zeitschrift Metabolites
Quellenangaben Band: 11, Heft: 6, Seiten: , Artikelnummer: 405 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen Novo Nordisk Fonden