L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2
Abstract
There is increasing evidence for a positive correlation between increases in plasma L-cysteine concentrations and the development and progression of type 2 diabetes (T2D) caused by obesity. Here, we show that prolonged treatment of mouse insulinoma 6 (MIN6) cells and mouse pancreatic islets with L-cysteine inhibited glucose-stimulated insulin secretion (GSIS). L-cysteine reversibly inactivated pyruvate kinase muscle isoform 2 (PKM2), an isoform of the rate-limiting enzyme pyruvate kinase in glycolysis, by inducing PKM2 subunit dissociation (tetramers to dimers/monomers), which resulted in impairment of glucose-induced ATP production and subsequent GSIS. Our findings in this work will raise caution about using a variety of L-cysteine containing supplements to diabetic patients and shed a light on a previously unidentified physiological role of L-cysteine and PKM2.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2015
- DOI:
- 10.1073/pnas.1417197112
- Bibcode:
- 2015PNAS..112E1067N