Herring R, Jones R H, Russell-Jones D L
Centre for Endocrinology, Diabetes and Research, Royal Surrey County Hospital, Guildford, UK.
Diabetes Obes Metab. 2014 Jan;16(1):1-8. doi: 10.1111/dom.12117. Epub 2013 May 16.
In spite of major developments in insulin production, purification, pharmaceutical formulation and methods of delivery, problems remain both in the day to day management of insulin-treated diabetes and with regard to its long-term complications. The risks of hypoglycaemia and weight gain are major concerns particularly for the patient, and the persistence of microvascular and premature macrovascular complications as the main causes of morbidity and mortality in both type 1 and type 2 diabetes is a constant reminder that our therapeutic and management strategies are inadequate. One clear and striking difference between currently available insulin treatments and normal physiology is the relative difference in exposure to insulin of the liver versus peripheral tissues. Hepatoselective insulin analogues have the potential to restore the normal hepatic to peripheral gradient in insulin action. Here, we discuss the possible therapeutic potential that such analogues may have over currently available insulin preparations. These benefits could include a lower risk of hypoglycaemia, less weight gain and a potential reduction in microvascular and macrovascular complications. We explore the evolution of insulin with hepatoselectivity in mind and possible strategies to create hepatoselective insulins.
尽管在胰岛素生产、纯化、药物制剂和给药方法方面取得了重大进展，但胰岛素治疗糖尿病的日常管理以及其长期并发症方面仍然存在问题。低血糖和体重增加的风险是患者尤其关注的主要问题，而微血管和过早出现的大血管并发症作为1型和2型糖尿病发病和死亡的主要原因持续存在，这不断提醒我们，我们的治疗和管理策略是不够的。目前可用的胰岛素治疗与正常生理之间一个明显且显著的差异是肝脏与外周组织所接触胰岛素的相对差异。肝选择性胰岛素类似物有可能恢复胰岛素作用中正常的肝脏与外周梯度。在此，我们讨论此类类似物相对于目前可用胰岛素制剂可能具有的治疗潜力。这些益处可能包括低血糖风险降低、体重增加减少以及微血管和大血管并发症可能减少。我们在考虑肝选择性的情况下探讨胰岛素的演变以及创建肝选择性胰岛素的可能策略。
