Sitagliptin does not improve isoprenaline-induced cardiac contractility in streptozotocin-induced diabetic rats

Ceren Uyar Boztas; Betül Rabia Erdoğan; Ayhanım Elif Müderrisoğlu; Gizem Kaykı Mutlu; Zeynep Elif Yeşilyurt Dirican; İrem Karaömerlioğlu; Vecdi Melih Altan; Ebru Arıoğlu İnan

Makale detayları

Sitagliptin does not improve isoprenaline-induced cardiac contractility in streptozotocin-induced diabetic rats

Yazarlar:

Ceren Uyar Boztas | Betül Rabia Erdoğan | Ayhanım Elif Müderrisoğlu | Gizem Kaykı Mutlu | Zeynep Elif Yeşilyurt Dirican | İrem Karaömerlioğlu | Vecdi Melih Altan | Ebru Arıoğlu İnan

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.359-367

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340664

pISSN:

2587-2087

Anahtar kelimeler:

Özet:

 Background and Aims: Sitagliptin, a dipeptidyl peptidase IV DPP-IV inhibitor, has been shown to have beneficial effects on the diabetic heart. Beta-adrenoceptor β-AR-mediated responses are impaired in diabetes. Our aim was to investigate the impact of sitagliptin on the diabetic rat heart in terms of β-AR-mediated responsiveness. In addition, we examined the expression of proteins associated with diastolic dysfunction and endoplasmic reticulum ER stress, as well as proteins involved in the β-AR signalling pathway. Methods: Eight-week-old Sprague-Dawley rats were divided into control, diabetic, and sitagliptin-treated 10 mgkgday for 4 weeks diabetic groups. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin STZ. Throughout the treatment period, the rats received sitagliptin orally. Cardiac β-AR responsiveness was assessed using in vitro papillary muscle experiments with a nonselective β-AR agonist, isoprenaline, and in vitro Langendorff heart preparation experiments with a β3-AR selective agonist CL 316,243. Western blot experiments were conducted to assess the protein expression of SERCA2a, GRP78, β3-AR, eNOS, and p-eNOS. Results: Sitagliptin did not reduce blood glucose levels or reverse weight loss in diabetic rats. However, it improved the heart weight to body weight ratio, indicating a reduction in cardiac hypertrophy. Sitagliptin did not correct the isoprenaline-induced contractile response in the diabetic group, nor did it alter the β3-AR mediated relaxation. Sitagliptin treatment also did not improve the downregulation of SERCA2a or the upregulation of GRP78. However, it reduced the upregulation of β3-AR. The protein expression of eNOS and the ratio of p-eNOS to eNOS were similar among the groups. Conclusion: This study indicates that sitagliptin treatment did not improve isoprenaline-mediated contractile responses or affect β3-AR-mediated relaxation in the diabetic heart. However, the observed increase in β3-AR protein expression in the diabetic heart treated with sitagliptin indicated a potential differential effect of the drug on this pathway compared to the β1-AR signalling pathway. Further studies are needed to elucidate the precise mechanisms by which sitagliptin influences β3-AR-mediated pathways.

 Background and Aims: Sitagliptin, a dipeptidyl peptidase IV DPP-IV inhibitor, has been shown to have beneficial effects on the diabetic heart. Beta-adrenoceptor β-AR-mediated responses are impaired in diabetes. Our aim was to investigate the impact of sitagliptin on the diabetic rat heart in terms of β-AR-mediated responsiveness. In addition, we examined the expression of proteins associated with diastolic dysfunction and endoplasmic reticulum ER stress, as well as proteins involved in the β-AR signalling pathway. Methods: Eight-week-old Sprague-Dawley rats were divided into control, diabetic, and sitagliptin-treated 10 mgkgday for 4 weeks diabetic groups. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin STZ. Throughout the treatment period, the rats received sitagliptin orally. Cardiac β-AR responsiveness was assessed using in vitro papillary muscle experiments with a nonselective β-AR agonist, isoprenaline, and in vitro Langendorff heart preparation experiments with a β3-AR selective agonist CL 316,243. Western blot experiments were conducted to assess the protein expression of SERCA2a, GRP78, β3-AR, eNOS, and p-eNOS. Results: Sitagliptin did not reduce blood glucose levels or reverse weight loss in diabetic rats. However, it improved the heart weight to body weight ratio, indicating a reduction in cardiac hypertrophy. Sitagliptin did not correct the isoprenaline-induced contractile response in the diabetic group, nor did it alter the β3-AR mediated relaxation. Sitagliptin treatment also did not improve the downregulation of SERCA2a or the upregulation of GRP78. However, it reduced the upregulation of β3-AR. The protein expression of eNOS and the ratio of p-eNOS to eNOS were similar among the groups. Conclusion: This study indicates that sitagliptin treatment did not improve isoprenaline-mediated contractile responses or affect β3-AR-mediated relaxation in the diabetic heart. However, the observed increase in β3-AR protein expression in the diabetic heart treated with sitagliptin indicated a potential differential effect of the drug on this pathway compared to the β1-AR signalling pathway. Further studies are needed to elucidate the precise mechanisms by which sitagliptin influences β3-AR-mediated pathways.

 Background and Aims: Sitagliptin, a dipeptidyl peptidase IV DPP-IV inhibitor, has been shown to have beneficial effects on the diabetic heart. Beta-adrenoceptor β-AR-mediated responses are impaired in diabetes. Our aim was to investigate the impact of sitagliptin on the diabetic rat heart in terms of β-AR-mediated responsiveness. In addition, we examined the expression of proteins associated with diastolic dysfunction and endoplasmic reticulum ER stress, as well as proteins involved in the β-AR signalling pathway. Methods: Eight-week-old Sprague-Dawley rats were divided into control, diabetic, and sitagliptin-treated 10 mgkgday for 4 weeks diabetic groups. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin STZ. Throughout the treatment period, the rats received sitagliptin orally. Cardiac β-AR responsiveness was assessed using in vitro papillary muscle experiments with a nonselective β-AR agonist, isoprenaline, and in vitro Langendorff heart preparation experiments with a β3-AR selective agonist CL 316,243. Western blot experiments were conducted to assess the protein expression of SERCA2a, GRP78, β3-AR, eNOS, and p-eNOS. Results: Sitagliptin did not reduce blood glucose levels or reverse weight loss in diabetic rats. However, it improved the heart weight to body weight ratio, indicating a reduction in cardiac hypertrophy. Sitagliptin did not correct the isoprenaline-induced contractile response in the diabetic group, nor did it alter the β3-AR mediated relaxation. Sitagliptin treatment also did not improve the downregulation of SERCA2a or the upregulation of GRP78. However, it reduced the upregulation of β3-AR. The protein expression of eNOS and the ratio of p-eNOS to eNOS were similar among the groups. Conclusion: This study indicates that sitagliptin treatment did not improve isoprenaline-mediated contractile responses or affect β3-AR-mediated relaxation in the diabetic heart. However, the observed increase in β3-AR protein expression in the diabetic heart treated with sitagliptin indicated a potential differential effect of the drug on this pathway compared to the β1-AR signalling pathway. Further studies are needed to elucidate the precise mechanisms by which sitagliptin influences β3-AR-mediated pathways.

 Background and Aims: Sitagliptin, a dipeptidyl peptidase IV DPP-IV inhibitor, has been shown to have beneficial effects on the diabetic heart. Beta-adrenoceptor β-AR-mediated responses are impaired in diabetes. Our aim was to investigate the impact of sitagliptin on the diabetic rat heart in terms of β-AR-mediated responsiveness. In addition, we examined the expression of proteins associated with diastolic dysfunction and endoplasmic reticulum ER stress, as well as proteins involved in the β-AR signalling pathway. Methods: Eight-week-old Sprague-Dawley rats were divided into control, diabetic, and sitagliptin-treated 10 mgkgday for 4 weeks diabetic groups. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin STZ. Throughout the treatment period, the rats received sitagliptin orally. Cardiac β-AR responsiveness was assessed using in vitro papillary muscle experiments with a nonselective β-AR agonist, isoprenaline, and in vitro Langendorff heart preparation experiments with a β3-AR selective agonist CL 316,243. Western blot experiments were conducted to assess the protein expression of SERCA2a, GRP78, β3-AR, eNOS, and p-eNOS. Results: Sitagliptin did not reduce blood glucose levels or reverse weight loss in diabetic rats. However, it improved the heart weight to body weight ratio, indicating a reduction in cardiac hypertrophy. Sitagliptin did not correct the isoprenaline-induced contractile response in the diabetic group, nor did it alter the β3-AR mediated relaxation. Sitagliptin treatment also did not improve the downregulation of SERCA2a or the upregulation of GRP78. However, it reduced the upregulation of β3-AR. The protein expression of eNOS and the ratio of p-eNOS to eNOS were similar among the groups. Conclusion: This study indicates that sitagliptin treatment did not improve isoprenaline-mediated contractile responses or affect β3-AR-mediated relaxation in the diabetic heart. However, the observed increase in β3-AR protein expression in the diabetic heart treated with sitagliptin indicated a potential differential effect of the drug on this pathway compared to the β1-AR signalling pathway. Further studies are needed to elucidate the precise mechanisms by which sitagliptin influences β3-AR-mediated pathways.

Makale detayları

Sitagliptin does not improve isoprenaline-induced cardiac contractility in streptozotocin-induced diabetic rats

Yazarlar:

Ceren Uyar Boztas | Betül Rabia Erdoğan | Ayhanım Elif Müderrisoğlu | Gizem Kaykı Mutlu | Zeynep Elif Yeşilyurt Dirican | İrem Karaömerlioğlu | Vecdi Melih Altan | Ebru Arıoğlu İnan

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.359-367

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340664

pISSN:

2587-2087

Beta adrenoceptor

Diabetes

Heart

Isoprenaline

Sitagliptin

Sayı

Makale detayları

Sitagliptin does not improve isoprenaline-induced cardiac contractility in streptozotocin-induced diabetic rats

Yazarlar: Ceren Uyar Boztas | Betül Rabia Erdoğan | Ayhanım Elif Müderrisoğlu | Gizem Kaykı Mutlu | Zeynep Elif Yeşilyurt Dirican | İrem Karaömerlioğlu | Vecdi Melih Altan | Ebru Arıoğlu İnan

Yayıncı: Istanbul University

Ana Başlıklar: Pharmacology and Pharmaceutical Sciences (Other)

Dergi: İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.359-367

Belge Tipi: Makale

Yayın Tarihi: 12/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001340664

pISSN: 2587-2087

Beta adrenoceptor

Diabetes

Heart

Isoprenaline

Sitagliptin

Sayı

Yazarlar:

Ceren Uyar Boztas | Betül Rabia Erdoğan | Ayhanım Elif Müderrisoğlu | Gizem Kaykı Mutlu | Zeynep Elif Yeşilyurt Dirican | İrem Karaömerlioğlu | Vecdi Melih Altan | Ebru Arıoğlu İnan

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.359-367

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340664

pISSN:

2587-2087