Groupe de recherche Jean-Christophe Jonas

EDIN

Pathophysiology of insulin-secreting pancreatic β-cells in type 2 diabetes

In type 2 diabetes, hyperglycaemia results from the combination of insulin resistance, defective insulin secretion, and increased glucagon secretion. Besides genetic risk factors, the reason why insulin-secreting β-cells fail to compensate for insulin resistance in some individuals may include lipotoxicity, low grade systemic inflammation and β-cell exhaustion. It is also clear that, once present, hyperglycaemia further reduces β-cell mass and function through a process called glucotoxicity.

Current research topics:

1) Impact of chronic changes in nutrient supply on the survival and function of insulin-secreting pancreatic β-cells. Recent projects focus on the glucotoxic alterations of β-cell function in human islets.

2) Role of redox changes at the subcellular level in the stimulation of insulin secretion by nutrients and its alterations under metabolic stress conditions (nutrient toxicity).

Selected Publications 2017-2019

Bensellam M, Shi YC, Chan JY, Laybutt DR, Chae H, Abou-Samra M, Pappas EG, Thomas HE, Gilon P and Jonas JC (2019) Metallothionein 1 negatively regulates glucose-stimulated insulin secretion and is
differentially expressed in conditions of beta-cell compensation and failure in mice and humans. Diabetologia, in press

Deglasse JP, Roma LP, Pastor-Flores D, Gilon P, Dick T, Jonas JC (2019) Glucose acutely reduces cytosolic and mitochondrial H2O2 in rat pancreatic beta-cells. Antioxid Redox Signal. 30: 297-313

Bensellam M, Jonas JC, Laybutt DR (2018) Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions. J Endocrinol 236: R109-R143

Santos LR, Muller C, Souza AH, Takahashi HK, Spégel P, Sweet IR, Chae H, Mulder H, Jonas JC (2017) NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic β-cells. Mol Metab 6: 535-547

Souza AH, Santos LR, Roma LP, Bensellam, Carpinelli AR, Jonas JC (2017) NADPH-oxidase oxidase-2 does not contribute to β-cell glucotoxicity in cultured pancreatic islets from C57BL/6J mice. Mol Cell Endocrinol 439: 354-362