PICK1-Deficient Mice Maintain Their Glucose Tolerance During Diet-Induced Obesity

Marie Balslev Backe, Rita Chan Andersen, Morten Jensen, Chunyu Jin, Cecilie Hundahl, Oksana Dmytriyeva, Jonas T Treebak, Jakob Bondo Hansen, Zach Gerhart-Hines, Kenneth L Madsen, Birgitte Holst*

*Corresponding author af dette arbejde


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 β-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 β-cell, whereby global PICK1-deficient mice resist further deterioration of their glucose tolerance following diet-induced obesity.

TidsskriftJournal of the Endocrine Society
Udgave nummer6
Sider (fra-til)bvad057
StatusUdgivet - 5 maj 2023


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