The Effects of Systemic and Local Acidosis on Insulin Resistance and Signaling
1
Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli IRCCS, 40136 Bologna, Italy
2
Department of Biomedical and Neuromotor Sciences, University of Bologna, 401223 Bologna, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 126; https://doi.org/10.3390/ijms20010126
Received: 13 October 2018
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Revised: 12 December 2018
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Accepted: 23 December 2018
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Published: 30 December 2018
(This article belongs to the Special Issue Insulin and Insulin Receptor in Diseases)
Most pathological conditions that cause local or systemic acidosis by overcoming the buffering activities of body fluids overlap with those diseases that are characterized by glucose metabolic disorders, including diabetes mellitus, inflammation, and cancer. This simple observation suggests the existence of a strong relationship between acidosis and insulin metabolism or insulin receptor signaling. In this review, we summarized the current knowledge on the activity of insulin on the induction of acidosis and, vice versa, on the effects of changes of extracellular and intracellular pH on insulin resistance. Insulin influences acidosis by promoting glycolysis. Although with an unclear mechanism, the lowering of pH, in turn, inhibits insulin sensitivity or activity. In addition to ketoacidosis that is frequently associated with diabetes, other important and more complex factors are involved in this delicate feedback mechanism. Among these, in this review we discussed the acid-mediated inhibiting effects on insulin binding affinity to its receptor, on glycolysis, on the recycling of glucose transporters, and on insulin secretion via transforming growth factor β (TGF-β) activity by pancreatic β-cells. Finally, we revised current data available on the mutual interaction between insulin signaling and the activity of ion/proton transporters and pH sensors, and on how acidosis may enhance insulin resistance through the Nuclear Factor kappa B (NF-κB) inflammatory pathway.
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Keywords:
insulin receptor; acidosis; glucose metabolism; ion/proton transporters; acid-sensing ion channels
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MDPI and ACS Style
Baldini, N.; Avnet, S. The Effects of Systemic and Local Acidosis on Insulin Resistance and Signaling. Int. J. Mol. Sci. 2019, 20, 126. https://doi.org/10.3390/ijms20010126
AMA Style
Baldini N, Avnet S. The Effects of Systemic and Local Acidosis on Insulin Resistance and Signaling. International Journal of Molecular Sciences. 2019; 20(1):126. https://doi.org/10.3390/ijms20010126
Chicago/Turabian StyleBaldini, Nicola, and Sofia Avnet. 2019. "The Effects of Systemic and Local Acidosis on Insulin Resistance and Signaling" International Journal of Molecular Sciences 20, no. 1: 126. https://doi.org/10.3390/ijms20010126
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