Ac3IV, a V1a and V1b receptor selective vasopressin analogue, protects against hydrocortisone-induced changes in pancreatic islet cell lineage
2022
Mohan, Shruti | Lafferty, Ryan A. | Flatt, P. R. (Peter R.) | Moffett, R Charlotte | Irwin, Nigel
The Avpr1a (V1a) and Avpr1b (V1b) receptor selective, vasopressin (AVP) analogue, Ac3IV has been shown to improve metabolism and pancreatic islet structure in diabetes and insulin resistance. The present study further investigates these actions by assessing the ability of Ac3IV to protect against pancreatic islet architectural disturbances induced by hydrocortisone (HC) treatment in transgenic Ins1Cʳᵉ/⁺;Rosa26-eYFP mice, that possess beta-cell lineage tracing capabilities. HC intervention increased (p < 0.001) energy intake but reduced (p < 0.01) body weight gain, with no impact of Ac3IV. All HC mice had reduced (p < 0.05) circulating glucose, but plasma insulin and glucagon concentrations remained unchanged. However, HC mice presented with increased (p < 0.001) pancreatic insulin content, which was further augmented by Ac3IV. In addition, Ac3IV treatment countered HC-induced increases in islet-, beta- and alpha-cell areas (p < 0.01), as well as promoting islet number towards control levels. This was accompanied by reduced (p < 0.05) beta-cell growth, but enhanced (p < 0.001) alpha-cell proliferation. There were no changes in islet cell apoptotic rates in any of the groups of HC mice, but co-expression of CK19 with insulin in pancreatic ductal cells was reduced by Ac3IV. Assessment of beta-cell lineage revealed that Ac3IV partially protected against HC-mediated de-differentiation of mature beta-cells, whilst also decreasing (p < 0.01) beta- to alpha-cell transdifferentiation. Our data indicate that sustained activation of V1a and V1b receptors exerts positive islet cell transition effects to help retain beta-cell identity in HC mice.
Mostrar más [+] Menos [-]Palabras clave de AGROVOC
Información bibliográfica
Este registro bibliográfico ha sido proporcionado por National Agricultural Library