Angiotensin II Type 1 Receptor Blockade Improves β-Cell Function and Glucose Tolerance in a Mouse Model of Type 2 Diabetes
Article Figures & Tables
Figures
- FIG. 1.
Immunohistochemical localization of AT1R and insulin in mouse pancreatic islets. A: AT1R immunoreactivity (red). B: Insulin immunoreactivity (blue). Insert: a merge image of AT1R and insulin in control islets. C: AT1R (red) in db/db islets. D: Insulin (blue) in db/db islets. Negative control for AT1R (E) and insulin (F) antibody. Magnification: Bar = 40 μm.
- FIG. 2.
Real-time RT-PCR analysis of AT1R mRNA expression in control and db/db islets. The relative expression was normalized as percentage of 18S rRNA calculated using the comparative threshold cycle method of 2−ΔΔCT. All data are expressed as means ± SE; n = 7 in each group. *P < 0.001 vs. control.
- FIG. 3.
Insulin release from isolated islets of control (ctl) and db/db mice. Effects of losartan (Los) and angiotensin II (AngII) on insulin release in 1.7 mmol/l (L) or 16.7 mmol/l (H) glucose from isolated islets of control mice (A) and db/db mice (B). C: Comparison of insulin release in control and diabetic mice. All values are given as means ± SE; n = 6–8 per group. *P < 0.05 vs. islets exposed to 1.7 mmol/l glucose only; †P < 0.05 vs. islets exposed to 16.7 mmol/l glucose only.
- FIG. 4.
(Pro)insulin biosynthesis from isolated islets of control (ctl) and diabetic mice. Effects of losartan (Los) and angiotensin II (AngII) on (pro)insulin biosynthesis in 1.7 mmol/l (L) or 16.7 mmol/l (H) glucose from isolated islets of control mice (A) and db/db mice (B). C: Comparison of (pro)insulin biosynthesis in control and db/db mice. All values are given as means ± SE; n = 5–8 each group. *P < 0.001 vs. islets exposed to 1.7 mmol/l glucose only; †P < 0.05 vs. islets exposed to 16.7 mmol/l glucose only.
- FIG. 5.
Effect of losartan on plasma glucose levels. A: 4-week-old db/db mice were treated with losartan (0, 1, 5, 10, or 20 mg · kg−1 · day−1 for 8 weeks, n = 6–10). B: Plasma glucose levels of control and db/db mice treated with 10 mg · kg−1 · day−1 losartan or water only were measured twice a week for 8 weeks from the age of 4 weeks. All values are given as means ± SE; n = 10–11 per group. *P < 0.05, **P < 0.01, and ***P < 0.001 vs. the corresponding animals treated with water only.
- FIG. 6.
Effect of daily losartan treatment (10 mg/kg) on OGTT in control and db/db mice. A: Plasma glucose concentrations in mice undergoing an OGTT (1 g/kg) after treatment with losartan or water only for 8 weeks. B: The areas under the curves (AUC) were expressed and compared. All values are given as means ± SE; n = 10–11 per group. *P < 0.001 vs. the corresponding animals treated with water only.
- FIG. 7.
Effect of daily losartan treatment (10 mg/kg) on insulin tolerance in db/db mice. Glucose concentrations in mice undergoing insulin tolerance test (intraperitoneal insulin injection 2 units/kg) after treatment with losartan or water only for 8 weeks did not differ significantly; n = 6 per group.
Tables
- TABLE 1
AT1R expression in control and db/db islets using the comparative threshold cycle method
Gene CT* ΔCT† ΔΔCT‡ Expression relative to control§ Control AT1R 26.52 ± 0.62 6.62 ± 0.48 18S 19.79 ± 0.53 Diabetes AT1R 24.54 ± 1.64 6.15 ± 0.76 −0.47 ± 0.77 3.06 18S 18.35 ± 0.95 Data are means ± SE.
- *
* Sample average of threshold cycle (CT) data.
- †
† The ΔCT value was calculated by the subtraction of the 18S rRNA CT from each sample CT.
- ‡
‡ The ΔΔCT value was calculated by subtraction of the control ΔCT from each transplanted sample ΔCT.
- §
§ Calculated using the equation 2−ΔΔCT.
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