Angiotensin-(1-7) Improves Islet Function in a Rat Model of Streptozotocin- Induced Diabetes Mellitus by Up-Regulating the Expression of Pdx1/Glut2.

Abstract

OBJECTIVE:

To observe the effects of angiotensin-(1-7) (Ang-(1-7)) on glucose metabolism, islet function and insulin resistance in a rat model of streptozotocin-induced diabetes mellitus (DM) and investigate its mechanism.

METHODS:

Thirty-four male Wistar rats were randomly divided into 3 groups: control group, which was fed a standard diet, DM group, high-fat diet and injected with streptozotocin, and Ang-(1-7) group receiving an injection of streptozotocin followed by Ang-(1-7) treatment. Blood glucose level, fasting serum Ang II and insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The pancreases were collected for histological examination, protein and gene expression analysis.

RESULTS:

Compared with the control group, fasting blood glucose, serum angiotensin II level, and HOMA-IR value increased, while serum insulin level decreased in the DM group. Moreover, islet structure was damaged, β cells were irregularly arranged, the cytoplasm was loose in the DM group. Expressions of Pancreatic duodenal homeobox-1 (Pdx1), glucose transporter-2 (Glut2) and glucokinase (Gk) were significantly decreased in the DM group compared with the control group. However, the DM-associated changes were dramatically reversed following Ang-(1-7) treatment.

CONCLUSION:

Ang-(1-7) protects against streptozotocin-induced DM through the improvement of insulin secretion, insulin resistance and islet fibrosis, which is associated with the upregulation of Pdx1, Glut2 and Gk expressions.

• Authors: Jingjing Li, Ruifang Zhu, Yalin Liu, Jinhui Yang, Xiaoyan Wang, Lisha Geng, Tingting Xu, Junhua He
• Journal: Endocrine, metabolic & immune disorders drug targets (Endocr Metab Immune Disord Drug Targets) Vol. 21 Issue 1 Pg. 156-162 ( 2021) ISSN: 2212-3873 [Electronic] United Arab Emirates
• PMID: 32679026 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Glucose Transporter Type 2
• Homeodomain Proteins
• Peptide Fragments
• Slc2a2 protein, rat
• Trans-Activators
• pancreatic and duodenal homeobox 1 protein
• Streptozocin
• Angiotensin I
• angiotensin I (1-7)

Topics

• Angiotensin I (pharmacology, therapeutic use)
• Animals
• Diabetes Mellitus, Experimental (chemically induced, drug therapy, genetics, physiopathology)
• Glucose Transporter Type 2 (genetics, metabolism)
• Homeodomain Proteins (genetics, metabolism)
• Insulin-Secreting Cells (drug effects, metabolism)
• Islets of Langerhans (drug effects, physiology)
• Male
• Peptide Fragments (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Streptozocin
• Trans-Activators (genetics, metabolism)
• Up-Regulation (drug effects, genetics)