Increased glucose sensitivity of stimulus-secretion coupling in islets from Psammomys obesus after diet induction of diabetes.

Pertusa, Jose A.G.;Nesher, Rafael;Kaiser, Nurit;Cerasi, Erol;Jonas, Jean-Christophe;et.al.
(2002) Diabetes — Vol. 51, n° 8, p. 2552-2560 (2002)

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Authors
  • Pertusa, Jose A.G.UCLouvain
    Author
  • Nesher, Rafael
    Author
  • Kaiser, Nurit
    Author
  • Cerasi, Erol
    Author
  • Henquin, Jean-ClaudeUCLouvain
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Abstract
When fed a high-energy (HE) diet, diabetes-prone (DP) Psammomys obesus develop type 2 diabetes with altered glucose-stimulated insulin secretion (GSIS). Beta-cell stimulus-secretion coupling was investigated in islets isolated from DP P. obesus fed a low-energy (LE) diet (DP-LE) and after 5 days on a HE diet (DP-HE). DP-LE islets cultured overnight in 5 mmol/l glucose displayed glucose dose-dependent increases in NAD(P)H, mitochondrial membrane potential, ATP/(ATP + ADP) ratio, cytosolic calcium concentration ([Ca(2+)](c)), and insulin secretion. In comparison, DP-HE islets cultured overnight in 10 mmol/l glucose were 80% degranulated and displayed an increased sensitivity to glucose at the level of glucose metabolism, [Ca(2+)](c), and insulin secretion. These changes in DP-HE islets were only marginally reversed after culture in 5 mmol/l glucose and were not reproduced in DP-LE islets cultured overnight in 10 mmol/l glucose, except for the 75% degranulation. Diabetes-resistant P. obesus remain normoglycemic on HE diet. Their beta-cell stimulus-secretion coupling was similar to that of DP-LE islets, irrespective of the type of diet. Thus, islets from diabetic P. obesus display an increased sensitivity to glucose at the level of glucose metabolism and a profound beta-cell degranulation, both of which may affect their in vivo GSIS.
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Pertusa, J. A. G., Nesher, R., Kaiser, N., Cerasi, E., Henquin, J.-C., & Jonas, J.-C. (2002). Increased glucose sensitivity of stimulus-secretion coupling in islets from Psammomys obesus after diet induction of diabetes. Diabetes, 51(8), 2552-2560. https://doi.org/10.2337/diabetes.51.8.2552 (Original work published 2002)