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Pancreatic adipocytes mediate hypersecretion of insulin in diabetes-susceptible mice

  • Objective: Ectopic fat accumulation in the pancreas in response to obesity and its implication on the onset of type 2 diabetes remain poorly understood. Intermittent fasting (IF) is known to improve glucose homeostasis and insulin resistance. However, the effects of IF on fat in the pancreas and beta-cell function remain largely unknown. Our aim was to evaluate the impact of IF on pancreatic fat accumulation and its effects on islet function. Methods: New Zealand Obese (NZO) mice were fed a high-fat diet ad libitum (NZO-AL) or fasted every other day (intermittent fasting, NZO-IF) and pancreatic fat accumulation, glucose homoeostasis, insulin sensitivity, and islet function were determined and compared to ad libitum-fed B6.V-Lep(ob/ob) (ob/ob) mice. To investigate the crosstalk of pancreatic adipocytes and islets, co-culture experiments were performed. Results: NZO-IF mice displayed better glucose homeostasis and lower fat accumulation in both the pancreas (-32%) and the liver (-35%) than NZO-AL mice. Ob/ob animals wereObjective: Ectopic fat accumulation in the pancreas in response to obesity and its implication on the onset of type 2 diabetes remain poorly understood. Intermittent fasting (IF) is known to improve glucose homeostasis and insulin resistance. However, the effects of IF on fat in the pancreas and beta-cell function remain largely unknown. Our aim was to evaluate the impact of IF on pancreatic fat accumulation and its effects on islet function. Methods: New Zealand Obese (NZO) mice were fed a high-fat diet ad libitum (NZO-AL) or fasted every other day (intermittent fasting, NZO-IF) and pancreatic fat accumulation, glucose homoeostasis, insulin sensitivity, and islet function were determined and compared to ad libitum-fed B6.V-Lep(ob/ob) (ob/ob) mice. To investigate the crosstalk of pancreatic adipocytes and islets, co-culture experiments were performed. Results: NZO-IF mice displayed better glucose homeostasis and lower fat accumulation in both the pancreas (-32%) and the liver (-35%) than NZO-AL mice. Ob/ob animals were insulin-resistant and had low fat in the pancreas but high fat in the liver. NZO-AL mice showed increased fat accumulation in both organs and exhibited an impaired islet function. Co-culture experiments demonstrated that pancreatic adipocytes induced a hypersecretion of insulin and released higher levels of free fatty adds than adipocytes of inguinal white adipose tissue. Conclusions: These results suggest that pancreatic fat participates in diabetes development, but can be prevented by IF. (C) 2019 Published by Elsevier Inc.show moreshow less

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Author details:Charline QuicletORCiD, Nicole Dittberner, Anneke Gaessler, Mandy StadionORCiDGND, Felicia GerstORCiDGND, Anett Helms, Christian BaumeierGND, Tim Julius SchulzORCiDGND, Annette SchurmannORCiDGND
DOI:https://doi.org/10.1016/j.metabol.2019.05.005
ISSN:0026-0495
ISSN:1532-8600
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/31108105
Title of parent work (English):Metabolism - Clinical and experimental
Publisher:Elsevier
Place of publishing:Philadelphia
Publication type:Article
Language:English
Year of first publication:2019
Publication year:2019
Release date:2020/12/10
Volume:97
Number of pages:9
First page:9
Last Page:17
Funding institution:German Ministry of Education and Research (BMBF: DZD)Federal Ministry of Education & Research (BMBF) [82DZD00302]; State of Brandenburg
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
DDC classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Peer review:Referiert
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