| First Author | Backe MB | Year | 2023 |
| Journal | J Endocr Soc | Volume | 7 |
| Issue | 6 | Pages | bvad057 |
| PubMed ID | 37200849 | Mgi Jnum | J:360764 |
| Mgi Id | MGI:7787268 | Doi | 10.1210/jendso/bvad057 |
| Citation | Backe MB, et al. (2023) PICK1-Deficient Mice Maintain Their Glucose Tolerance During Diet-Induced Obesity. J Endocr Soc 7(6):bvad057 |
| abstractText | CONTEXT: Metabolic disorders such as obesity represent a major health challenge. Obesity alone has reached epidemic proportions, with at least 2.8 million people worldwide dying annually from diseases caused by overweight or obesity. The brain-metabolic axis is central to maintain homeostasis under metabolic stress via an intricate signaling network of hormones. Protein interacting with C kinase 1 (PICK1) is important for the biogenesis of various secretory vesicles, and we have previously shown that PICK1-deficient mice have impaired secretion of insulin and growth hormone. 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. 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. 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 beta-cell-specific knockdown of PICK1 showed impaired glucose tolerance both on chow and HFD similar to WT mice. CONCLUSION: Our findings support the importance of PICK1 in overall hormone regulation. However, importantly, this effect is independent of the PICK1 expression in the beta-cell, whereby global PICK1-deficient mice resist further deterioration of their glucose tolerance following diet-induced obesity. |
