Conclusion
Our findings support the importance of PICK1 in overall hormone regulation. However, importantly, this effect is independent of the PICK1 expression in the β-cell, whereby global PICK1-deficient mice resist further deterioration of their glucose tolerance following diet-induced obesity.
Methods
We characterized the metabolic phenotype through assessment of body weight, composition, glucose tolerance, islet morphology insulin secretion in vivo, and glucose-stimulated insulin secretion ex vivo.
Objective
The aim was to investigate how global PICK1-deficient mice respond to high-fat diet (HFD) and assess its role in insulin secretion in diet-induced obesity.
Results
PICK1-deficient mice displayed similar weight gain and body composition as wild-type (WT) mice following HFD. While HFD impaired glucose tolerance of WT mice, PICK1-deficient mice were resistant to further deterioration of their glucose tolerance compared with already glucose-impaired chow-fed PICK1-deficient mice. Surprisingly, mice with β-cell-specific knockdown of PICK1 showed impaired glucose tolerance both on chow and HFD similar to WT mice.