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Efficacy of lanthionine‐stabilized angiotensin‐(1–7) in type I and type II diabetes mouse models

A. Kuipers,G. Moll,E. Wagner,R. Franklin

Published 2019 in Peptides

ABSTRACT

HIGHLIGHTSLanthionine‐stabilized angiotensin‐(1–7) is effective in glycemic control.cAng‐(1–7) recovers insulin levels in mouse models of type I and II diabetes.cAng‐(1–7) lowers glucose levels in mouse models of type I and II diabetes. ABSTRACT Native angiotensin‐(1–7) exerts many therapeutic effects. However, it is rapidly degraded by ACE and other peptidases. This drawback is largely eliminated for lanthionine‐stabilized angiotensin‐(1–7), termed cAng‐(1–7), which is fully resistant to ACE and has strongly increased resistance to other peptidases. Goal of the present study was to test whether cAng‐(1–7) has therapeutic activity in diabetes mouse models: in a multiple low dose streptozotocin‐induced model of type I diabetes and / or in a db/db model of type II diabetes. In the type I diabetes model cAng‐(1–7) caused in an increase in the insulin level of 133% in week 4 (p < 0.001) compared to vehicle, and in the type II diabetes model an increase of 55% of the insulin level in week 8 (p < 0.05) compared to vehicle. cAng‐(1–7) reduced blood glucose levels in the type I model by 37% at day 22 (p < 0.001) and in the type II diabetes model by 17% at day 63 of treatment (p < 0.001) and in an oral glucose tolerance test in a type II diabetes model, by 17% at week 4 (p < 0.01). cAng‐(1–7) also caused a reduction of glycated hemoglobin levels in the type II diabetes model of 21% in week 6 (p < 0,001). These data are consistent with therapeutic potential of cAng‐(1–7) in type I and II diabetes.

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