GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through
activation of the PI3K/Akt pathway
J. Clin. Invest. Mallappa Anitha, et al. 116:344 doi:10.1172/JCI26295 [
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Figure 1Hyperglycemia induces apoptosis in enteric neurons, and this is ameliorated by GDNF. To study the dose-dependent effects of hyperglycemia, different concentrations of glucose (5, 10, or 20 mM) were used in serum-free/glucose-free media. (
A) Apoptosis was assessed by the Ret/Hoechst staining method. (
B) Magnified view of neurons to show the DNA fragmentation (arrow) seen during apoptosis compared with a healthy neuron (on the right). (
C) Apoptosis was assessed using the Ret/TUNEL method in the presence or absence of GDNF and the stated glucose or mannitol concentrations. (
D) Representative photomicrographs of enteric neurons cultured in the presence of 5 mM and 20 mM glucose and assessed for apoptosis using the Ret/TUNEL method. Ret (red) staining was used as a neuronal marker. Arrows identify the apoptotic cells (yellow) with condensed nuclei. Figure shows results of 4 independent experiments. *
P < 0.05; **
P < 0.01; ***
P < 0.001. Scale bars: 20 μm (
B); 100 μm (
D). Glu, glucose.
