PMID- 35037128 OWN - NLM STAT- MEDLINE DCOM- 20220413 LR - 20220531 IS - 1432-119X (Electronic) IS - 0948-6143 (Linking) VI - 157 IP - 4 DP - 2022 Apr TI - Morphological alteration of the pancreatic islet in ovariectomized rats fed a high-fat high-fructose diet. PG - 427-442 LID - 10.1007/s00418-021-02062-0 [doi] AB - Diabetes and its complications are major causes of mortality worldwide. Type 2 diabetes coexists with insulin resistance and beta-cell dysfunction, which are aggravated by overconsumption and estrogen-deprived conditions. However, the morphology of pancreatic islets in a combined condition of excessive caloric intake and estrogen deficiency has never been described. Herein, we examined morphological changes in the pancreatic islets of ovariectomized (OVX) rats fed a high-fat high-fructose diet (HFFD) for 12 weeks. The histological changes in the size and number of pancreatic islets were assessed by hematoxylin-eosin and immunohistochemical staining. Enlarged pancreatic islets with fat deposition in OVX rats were accompanied by whole-body insulin resistance and hyperglycemia. The addition of a HFFD to OVX rats (OVX + HFFD) further aggravated insulin resistance, with a substantial increase in the density of enlarged pancreatic islets and fat accumulation. The augmented number of enlarged islets was correlated with elevated plasma glucose and insulin levels. Intriguingly, unlike the HFFD and OVX alone, the OVX + HFFD markedly expanded the area of insulin-producing beta-cells and glucagon-producing alpha-cells. Importantly, enlarged islets, pancreatic fat deposits, and diabetic states developing in OVX + HFFD conditions were resolved by estrogen replacement. Collectively, the morphological characteristics of pancreatic islets were influenced in an insulin-resistant state caused by estrogen deficiency and HFFD consumption and were distinct from each factor alone. A combination of estrogen deficiency with HFFD consumption worsened the integrity of pancreatic islets, ultimately resulting in disease progression. These findings expand our understanding of the causal relationship between pancreatic morphology and diabetes development and suggest therapeutic strategies. CI - (c) 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Chansela, Piyachat AU - Chansela P AD - Department of Anatomy, Phramongkutklao College of Medicine, Bangkok, 10400, Thailand. FAU - Potip, Bubphachat AU - Potip B AD - Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. FAU - Weerachayaphorn, Jittima AU - Weerachayaphorn J AD - Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. FAU - Kangwanrangsan, Niwat AU - Kangwanrangsan N AD - Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. FAU - Chukijrungroat, Natsasi AU - Chukijrungroat N AD - Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. FAU - Saengsirisuwan, Vitoon AU - Saengsirisuwan V AUID- ORCID: 0000-0001-7798-3680 AD - Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. vitoon.sae@mahidol.ac.th. LA - eng GR - RSA-5780009/Thailand Research Fund/ GR - RSA-6080072/Thailand Research Fund/ PT - Journal Article DEP - 20220117 PL - Germany TA - Histochem Cell Biol JT - Histochemistry and cell biology JID - 9506663 RN - 0 (Estrogens) RN - 0 (Insulin) RN - 30237-26-4 (Fructose) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/pathology MH - Diet, High-Fat/adverse effects MH - Estrogens MH - Female MH - Fructose MH - Insulin MH - *Insulin Resistance MH - *Islets of Langerhans/pathology MH - Rats OTO - NOTNLM OT - Estrogen OT - High-fat high-fructose diet OT - Insulin resistance OT - Pancreatic beta-cells EDAT- 2022/01/18 06:00 MHDA- 2022/04/14 06:00 CRDT- 2022/01/17 06:19 PHST- 2021/11/30 00:00 [accepted] PHST- 2022/01/18 06:00 [pubmed] PHST- 2022/04/14 06:00 [medline] PHST- 2022/01/17 06:19 [entrez] AID - 10.1007/s00418-021-02062-0 [pii] AID - 10.1007/s00418-021-02062-0 [doi] PST - ppublish SO - Histochem Cell Biol. 2022 Apr;157(4):427-442. doi: 10.1007/s00418-021-02062-0. Epub 2022 Jan 17.