Fig. 3.

A holistic summary and illustration of the crosstalk between PTMs and diabetes. The pathogenesis of diabetes is complex and interactive, involving various cellular responses and signaling cascades regulated by PTMs. (1) Balance the actions of kinases and phosphatases in regulating glucose-stimulated insulin secretion from pancreatic beta cells. (2) Establish the link between gluconeogenesis, the TCA cycle and glycolysis. (3) Directly cause modification of certain proteins or induce PTMs secondary to various cellular processes to maintain beta cell function and viability. Different colors and shapes represent different types of PTMs. Activation and inhibition effects are displayed in “arrows” and “inhibition” symbols, respectively. The figure is generated with BioRender (https://biorender.com). CUL4A cullin 4A, ERK extracellular regulated protein kinases, FOXO1 forkhead box O1, GCK glucokinase, GLUT glucose transporter, GSK-3 glycogen synthase kinase 3, IRS insulin receptor substrate, HDAC histone deacetylase inhibitor, JNK c-Jun N-terminal kinase, MKP1 mitogen-activated protein kinase phosphatase, MEKK mitogen-activated extracellular signal-regulated kinase kinase, NF-κB nuclear factor-k-gene binding, PTP1B protein tyrosine phosphatase 1B, PTEN phosphatase and tensin homolog, PPAR peroxisome proliferators-activated receptors, PDK1 3-phosphoinositide-dependent protein kinase 1, PP2A proteinphosphatase2A, SENP2 sentrin-specific protease 2, SREBP1 sterol-regulatory element binding protein 1, SIRT sirtuins, TRIB3 tribbles pseudokinase 3, TXNIP thioredoxin interacting protein