Amylin Analogues in the Treatment of Diabetes Mellitus: Medicinal Chemistry and Structural Basis of its Function



Ernest Adeghate*, 1, Huba Kalász2
1 Department of Anatomy, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
2 Department of Pharmacology and Therapeutics, Semmelweis University, Budapest, Hungary


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© Adeghate and Kalász; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates; Fax: +971-3-7672033; E-mail: eadeghate@uaeu.ac.ae


Abstract

Amylin, (islet amyloid polypeptide) or diabetes-associated peptide is co-secreted with insulin in the islet of Langerhans of diabetic patients in approximately 1:100, amylin-insulin ratio. The soluble form of amylin, an analogue of amylin, is used as a supplement to insulin in the treatment of type 1 diabetes. Co-administration of amylin analogue with insulin to patients with type 1 diabetes induced a larger reduction in proprandial hyperglycemia, with a concomitant reduction in the level of glucagon when compared to insulin monotherapy. The actions of amylin analogues appear to be synergistic to insulin, with which it is co-released from insulin-producing beta cells after a meal. Amylin analogues such as pramlintide has been shown to significantly reduce body weight, HbA1c values and even the dosage of insulin. A moderate weight loss can also be achieved in obese patients with or without diabetes. A major side effect of some amylin analogues includes nausea and excitation of the area postrema. This review examines the medicinal chemistry of amylin and its analogues and their effects.

Keywords: Amylin, type 1 diabetes, medicinal chemistry, pramlintide.