Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats
Diabetes mellitus type 2 (DM2) is a disease with increasing importance in modern societies and insufficient treatment options. Pharmacological stimulation of insulin signaling, which is blunted in DM2, is a promising approach to treat this disease. It has been shown that activation of the angiotensi...
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2014
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09462716_v92_n3_p255_Santos http://hdl.handle.net/20.500.12110/paper_09462716_v92_n3_p255_Santos |
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paper:paper_09462716_v92_n3_p255_Santos2023-06-08T15:53:53Z Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats Angiotensin-(1-7) Antidiabetic Diabetes RNA interference 2 hydroxypropyl beta cyclodextrin angiotensin[1-7] glucose glucose transporter 4 glycogen synthase kinase 3beta insulin insulin receptor insulin receptor substrate 1 protein kinase B animal cell animal cell culture animal experiment animal model animal tissue antidiabetic activity article body weight cell isolation cell membrane controlled study diabetic nephropathy diuresis down regulation drug formulation enzyme phosphorylation glucose blood level glucose transport heart muscle cell histology hyperglycemia immunoblotting in vitro study insulin blood level insulin resistance insulin sensitivity long term care male newborn non insulin dependent diabetes mellitus nonhuman prevention study rat signal transduction therapy effect urine volume Administration, Oral Angiotensin I Animals Animals, Newborn Deoxyglucose Diabetes Mellitus, Type 2 Hyperglycemia Hypoglycemic Agents Insulin Male Myocytes, Cardiac Peptide Fragments Phosphorylation Proto-Oncogene Proteins c-akt Rats Rats, Sprague-Dawley Signal Transduction Diabetes mellitus type 2 (DM2) is a disease with increasing importance in modern societies and insufficient treatment options. Pharmacological stimulation of insulin signaling, which is blunted in DM2, is a promising approach to treat this disease. It has been shown that activation of the angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system leads to an improved glucose uptake. In this study, we intended to evaluate, whether this effect could be exploited therapeutically. We first confirmed that Ang-(1-7) improves insulin signaling and glucose uptake in vitro in cultured cardiomyocytes. We then evaluated the therapeutic effect of a newly developed hydro-xypropyl- β-cyclodextrin-based Ang-(1-7) nano-formulation in a novel transgenic rat model of inducible insulin resistance and DM2. The chronic administration of this compound prevented the marked elevation in blood glucose levels in these rats at a dose of 30 μg/kg, reversed the established hyperglycemic state at a dose of 100 μg/kg, and resulted in improved insulin sensitivity, reduced plasma insulin and decreased diabetic nephropathy. In conclusion, an oral Ang-(1-7) formulation reverses hyperglycemia and its consequences in an animal model of DM2 and represents a novel therapeutic option for the treatment of DM2 and other cardio-metabolic diseases. Key message: A novel rat model with inducible diabetes can be used to evaluate new therapies. Angiotensin-(1-7) is effective in an oral formulation packaged in cyclodextrine. Angiotensin-(1-7) is a promising antidiabetic drug. © 2013 Springer-Verlag Berlin Heidelberg. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09462716_v92_n3_p255_Santos http://hdl.handle.net/20.500.12110/paper_09462716_v92_n3_p255_Santos |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Angiotensin-(1-7) Antidiabetic Diabetes RNA interference 2 hydroxypropyl beta cyclodextrin angiotensin[1-7] glucose glucose transporter 4 glycogen synthase kinase 3beta insulin insulin receptor insulin receptor substrate 1 protein kinase B animal cell animal cell culture animal experiment animal model animal tissue antidiabetic activity article body weight cell isolation cell membrane controlled study diabetic nephropathy diuresis down regulation drug formulation enzyme phosphorylation glucose blood level glucose transport heart muscle cell histology hyperglycemia immunoblotting in vitro study insulin blood level insulin resistance insulin sensitivity long term care male newborn non insulin dependent diabetes mellitus nonhuman prevention study rat signal transduction therapy effect urine volume Administration, Oral Angiotensin I Animals Animals, Newborn Deoxyglucose Diabetes Mellitus, Type 2 Hyperglycemia Hypoglycemic Agents Insulin Male Myocytes, Cardiac Peptide Fragments Phosphorylation Proto-Oncogene Proteins c-akt Rats Rats, Sprague-Dawley Signal Transduction |
| spellingShingle |
Angiotensin-(1-7) Antidiabetic Diabetes RNA interference 2 hydroxypropyl beta cyclodextrin angiotensin[1-7] glucose glucose transporter 4 glycogen synthase kinase 3beta insulin insulin receptor insulin receptor substrate 1 protein kinase B animal cell animal cell culture animal experiment animal model animal tissue antidiabetic activity article body weight cell isolation cell membrane controlled study diabetic nephropathy diuresis down regulation drug formulation enzyme phosphorylation glucose blood level glucose transport heart muscle cell histology hyperglycemia immunoblotting in vitro study insulin blood level insulin resistance insulin sensitivity long term care male newborn non insulin dependent diabetes mellitus nonhuman prevention study rat signal transduction therapy effect urine volume Administration, Oral Angiotensin I Animals Animals, Newborn Deoxyglucose Diabetes Mellitus, Type 2 Hyperglycemia Hypoglycemic Agents Insulin Male Myocytes, Cardiac Peptide Fragments Phosphorylation Proto-Oncogene Proteins c-akt Rats Rats, Sprague-Dawley Signal Transduction Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
| topic_facet |
Angiotensin-(1-7) Antidiabetic Diabetes RNA interference 2 hydroxypropyl beta cyclodextrin angiotensin[1-7] glucose glucose transporter 4 glycogen synthase kinase 3beta insulin insulin receptor insulin receptor substrate 1 protein kinase B animal cell animal cell culture animal experiment animal model animal tissue antidiabetic activity article body weight cell isolation cell membrane controlled study diabetic nephropathy diuresis down regulation drug formulation enzyme phosphorylation glucose blood level glucose transport heart muscle cell histology hyperglycemia immunoblotting in vitro study insulin blood level insulin resistance insulin sensitivity long term care male newborn non insulin dependent diabetes mellitus nonhuman prevention study rat signal transduction therapy effect urine volume Administration, Oral Angiotensin I Animals Animals, Newborn Deoxyglucose Diabetes Mellitus, Type 2 Hyperglycemia Hypoglycemic Agents Insulin Male Myocytes, Cardiac Peptide Fragments Phosphorylation Proto-Oncogene Proteins c-akt Rats Rats, Sprague-Dawley Signal Transduction |
| description |
Diabetes mellitus type 2 (DM2) is a disease with increasing importance in modern societies and insufficient treatment options. Pharmacological stimulation of insulin signaling, which is blunted in DM2, is a promising approach to treat this disease. It has been shown that activation of the angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system leads to an improved glucose uptake. In this study, we intended to evaluate, whether this effect could be exploited therapeutically. We first confirmed that Ang-(1-7) improves insulin signaling and glucose uptake in vitro in cultured cardiomyocytes. We then evaluated the therapeutic effect of a newly developed hydro-xypropyl- β-cyclodextrin-based Ang-(1-7) nano-formulation in a novel transgenic rat model of inducible insulin resistance and DM2. The chronic administration of this compound prevented the marked elevation in blood glucose levels in these rats at a dose of 30 μg/kg, reversed the established hyperglycemic state at a dose of 100 μg/kg, and resulted in improved insulin sensitivity, reduced plasma insulin and decreased diabetic nephropathy. In conclusion, an oral Ang-(1-7) formulation reverses hyperglycemia and its consequences in an animal model of DM2 and represents a novel therapeutic option for the treatment of DM2 and other cardio-metabolic diseases. Key message: A novel rat model with inducible diabetes can be used to evaluate new therapies. Angiotensin-(1-7) is effective in an oral formulation packaged in cyclodextrine. Angiotensin-(1-7) is a promising antidiabetic drug. © 2013 Springer-Verlag Berlin Heidelberg. |
| title |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
| title_short |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
| title_full |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
| title_fullStr |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
| title_full_unstemmed |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
| title_sort |
oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09462716_v92_n3_p255_Santos http://hdl.handle.net/20.500.12110/paper_09462716_v92_n3_p255_Santos |
| _version_ |
1768542184905113600 |