The challenging organ interplay in diabetes management
Diabetes is a complex metabolic disorder characterized by elevated blood sugar levels, primarily caused by insufficient insulin production to meet the need of insulin signaling to its target organs. While the pancreas and its beta-cells are central to insulin secretion for sugar regulation, other organs such as the liver also play a significant role in diabetes.
The effects of Zaprinast in the liver…
A few years ago, the research team led by Pr. Jean-Claude Martinou discovered a cellular transporter involved in the energy supply of the mitochondria, the MPC. As this transporter is involved in the sugar equilibrium of the body, researchers from the laboratory of Pr. Pierre Maechler decided to explore the potential of inhibiting MPC to treat diabetes. Among hundreds of compounds tested, Zaprinast showed promise as an efficient inhibitor of MPC: in vitro and in vivo experiments confirmed that Zaprinast blocks sugar production by the liver, which is known to contribute to high blood glucose in diabetes.
… are counterbalanced in the pancreas
Surprisingly, Zaprinast, while effective in inhibiting liver glucose production, failed to normalize blood sugar levels in diabetic mice. This paradoxical outcome stems from the intricate reliance of both the liver and the endocrine pancreas on MPC: the positive impact in the liver is counterbalanced by an opposing action in the pancreas, resulting in null effect overall on blood glucose.
This research is of considerable significance as it highlights the complex interplay between organs in metabolic pathologies. Incidentally, it underlines the critical importance of conducting in vivo studies to comprehend the multifaceted mechanisms at play in multi-organ diseases like diabetes.
Zaprinast blocks sugar production by the liver but fails to normalize diabetic blood glucose levels. © Abcam
Interested to learn more
To learn more about the recent advances of UNIGE researchers in the field of diabetes, feel free to join them on the Diabetes Open Day on Thursday 7th of November. >>> All information on the website
3 Nov 2023