Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats
Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry an...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Marisa Esteves-Monteiro Daniela Menezes-Pinto Mariana Ferreira-Duarte Patrícia Dias-Pereira Manuela Morato Margarida Duarte-Araújo |
| author_facet | Marisa Esteves-Monteiro Daniela Menezes-Pinto Mariana Ferreira-Duarte Patrícia Dias-Pereira Manuela Morato Margarida Duarte-Araújo |
| author_sort | Marisa Esteves-Monteiro |
| collection | DOAJ |
| description | Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility. |
| first_indexed | 2024-03-09T19:00:32Z |
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| id | doaj.art-5dfad9e35b5a41528bd0ea8ca0e67a1b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:00:32Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5dfad9e35b5a41528bd0ea8ca0e67a1b2023-11-24T05:04:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211323310.3390/ijms232113233Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic RatsMarisa Esteves-Monteiro0Daniela Menezes-Pinto1Mariana Ferreira-Duarte2Patrícia Dias-Pereira3Manuela Morato4Margarida Duarte-Araújo5LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLaboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, PortugalLAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalDepartment of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, PortugalLAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalDiabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility.https://www.mdpi.com/1422-0067/23/21/13233diabetes mellitusSTZileum histomorphometrycolon histomorphometrysmooth muscle contractionAngiotensin II receptors |
| spellingShingle | Marisa Esteves-Monteiro Daniela Menezes-Pinto Mariana Ferreira-Duarte Patrícia Dias-Pereira Manuela Morato Margarida Duarte-Araújo Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats International Journal of Molecular Sciences diabetes mellitus STZ ileum histomorphometry colon histomorphometry smooth muscle contraction Angiotensin II receptors |
| title | Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats |
| title_full | Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats |
| title_fullStr | Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats |
| title_full_unstemmed | Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats |
| title_short | Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats |
| title_sort | histomorphometry changes and decreased reactivity to angiotensin ii in the ileum and colon of streptozotocin induced diabetic rats |
| topic | diabetes mellitus STZ ileum histomorphometry colon histomorphometry smooth muscle contraction Angiotensin II receptors |
| url | https://www.mdpi.com/1422-0067/23/21/13233 |
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