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

• Published in: Peptides (New York, N.Y. : 1980) Vol. 112; pp. 78 - 84
• Main Authors: Kuipers, Anneke, Moll, Gert N., Wagner, Elizabeth, Franklin, Rick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2019
• Subjects: Angiotensin; Diabetes; Glucose; Insulin; Lanthipeptide; Diabetes; Glucose; Lanthipeptide; Insulin; Angiotensin
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2018.10.015

•Lanthionine-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. 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.