TY - JOUR A1 - Quiclet, Charline A1 - Dittberner, Nicole A1 - Gaessler, Anneke A1 - Stadion, Mandy A1 - Gerst, Felicia A1 - Helms, Anett A1 - Baumeier, Christian A1 - Schulz, Tim Julius A1 - Schurmann, Annette T1 - Pancreatic adipocytes mediate hypersecretion of insulin in diabetes-susceptible mice JF - Metabolism - Clinical and experimental N2 - 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 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. Y1 - 2019 U6 - https://doi.org/10.1016/j.metabol.2019.05.005 SN - 0026-0495 SN - 1532-8600 VL - 97 SP - 9 EP - 17 PB - Elsevier CY - Philadelphia ER - TY - JOUR A1 - Jonas, Wenke A1 - Kluth, Oliver A1 - Helms, Anett A1 - Voss, Sarah A1 - Jahnert, Markus A1 - Gottmann, Pascal A1 - Speckmann, Thilo A1 - Knebel, Birgit A1 - Chadt, Alexandra A1 - Al-Hasani, Hadi A1 - Schürmann, Annette A1 - Vogel, Heike T1 - Identification of novel genes involved in hyperglycemia in mice JF - International journal of molecular sciences N2 - Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function. KW - beta-cell KW - diabetes KW - proliferation KW - apoptosis KW - QTL Y1 - 2022 U6 - https://doi.org/10.3390/ijms23063205 SN - 1661-6596 SN - 1422-0067 VL - 23 IS - 6 PB - MDPI CY - Basel ER -