TY - JOUR

T1 - PICK1-Deficient Mice Maintain Their Glucose Tolerance During Diet-Induced Obesity

AU - Backe, Marie Balslev

AU - Andersen, Rita Chan

AU - Jensen, Morten

AU - Jin, Chunyu

AU - Hundahl, Cecilie

AU - Dmytriyeva, Oksana

AU - Treebak, Jonas T

AU - Hansen, Jakob Bondo

AU - Gerhart-hines, Zach

AU - Madsen, Kenneth L

AU - Holst, Birgitte

PY - 2023

Y1 - 2023

N2 - ContextMetabolic 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.ObjectiveThe 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.MethodsWe 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.ResultsPICK1-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.ConclusionOur 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.

AB - ContextMetabolic 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.ObjectiveThe 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.MethodsWe 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.ResultsPICK1-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.ConclusionOur 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.

U2 - 10.1210/jendso/bvad057

DO - 10.1210/jendso/bvad057

M3 - Journal article

C2 - 37200849

VL - 7

SP - 1

EP - 13

JO - Journal of the endocrine society

JF - Journal of the endocrine society

SN - 2472-1972

IS - 6

M1 - bvad057

ER -