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Morphological alteration of the pancreatic islet in ovariectomized rats fed a high-fat high-fructose diet

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Diabetes and its complications are major causes of mortality worldwide. Type 2 diabetes coexists with insulin resistance and β-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 β-cells and glucagon-producing α-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.

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Type 2 diabetes mellitus




High-fat high-fructose diet


Oral glucose tolerance test


Free fatty acids


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This study was partly supported by Mahidol University and the Thailand Research Fund (RSA-5780009 to VS and RSA-6080072 to JW).

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PC, NC, JW and VS conceived of the study, participated in its design and coordination. NC and VS performed animal handling and tissue collection. PC and BP carried out tissue processing and immunohistochemistry experiments, performed evaluation and the statistical analysis for immunohistochemistry. PC, JW and NK performed TUNEL assay. PC, JW and VS analyzed and interpreted the results. PC drafted the manuscript. PC, BP and JW prepared the figures for the manuscript. PC, JW and VS edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Vitoon Saengsirisuwan.

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The authors declare that they have no conflicts of interest.

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The animal protocols for this study were approved by the Institutional Animal Care and Use Committee of the Faculty of Science, Mahidol University (animal protocol numbers: MUSC56-033-295 and MUSC60-017-367) in accordance with the International Guiding Principles for Biomedical Research Involving Animals of the Council for International Organizations of Medical Sciences.

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Chansela, P., Potip, B., Weerachayaphorn, J. et al. Morphological alteration of the pancreatic islet in ovariectomized rats fed a high-fat high-fructose diet. Histochem Cell Biol 157, 427–442 (2022).

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