Schematic outline of a 5‐HT‐dependent mechanism inducing changes in insulin (Ins1/2 in mouse) production independently or through the transcription factor Pet1/Fev. Note that 5‐HT receptors (5HTRx, non‐specified subclass) could contribute by affecting regulatory genes upstream from either Pet1/Fev or Ins1/2, or both. Likewise, the serotonin transporter (SERT) could affect Pet1/Fev or Ins1/2 directly or through upstream regulatory elements (indirect cascade).
Ex vivo treatment with psychostimulants but 5‐HT significantly decreased both Pet1/Fev (left) and Ins2 (middle) mRNA levels in fetal pancreatic explants. In these experiments, Pet1/Fev and Ins2 mRNA expression positively correlated (right).
None of the treatments affected glucagon (Gcg) expression, which did not correlate with that of Pet1/Fev either (C1).
Pet1/Fev expression (left) and its correlation with Ins2 in 6‐week‐old offspring prenatally exposed to the psychostimulants indicated.
Positive Spearman's correlation between PET1/FEV and INS but not GCG mRNA levels in pancreatic islets form healthy (normoglycemic; NGT in black) and diabetic donors (impaired glucose tolerance (IGT; blue) and diabetic (T2D; gray)). Data were expressed as log2 fragments per kilobase million (FPKM).
Data information: Quantitative data from
n ≥ 3 explants or mice/group were expressed as means ± SD, ***
P < 0.001, **
P < 0.01, *
P < 0.05 (pair‐wise comparison after one‐way ANOVA).
