Pramlintide: An Amylin Analogue Protects Endothelial Cells against Oxidative Stress through Regulating Oxidative Markers and NF‑κb Expression

Leila Safaeian, Fatemeh Shafiee, Marzieh Naderi


Background: Oxidative stress has a prominent role in the pathogenesis of diabetes complications. Pramlintide is an injectional amylin analogue used for the treatment of type 1 and type 2 diabetic patients. The present investigation evaluated the effect of pramlintide against oxidative damage induced by hydrogen peroxide (H2 O2 ) in human umbilical vein endothelial cells (HUVECs). Methods: Cell viability was assessed using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide method. Hydroperoxides level, ferric reducing antioxidant power (FRAP), and expression of transcription factor NF‑κB were measured in HUVECs that pretreated with pramlintide and, then exposed to H2 O2 . Results: Pramlintide significantly decreased the cytotoxicity caused by H2 O2 at the concentrations of 5 and 10 µg/mL. Pretreatment of HUVECs with pramlintide reduced hydroperoxides and increased FRAP value in intra‑ and extra‑cellular mediums at different concentration ranges compared with H2 O2 stimulated cells. Pramlintide (10 µg/mL) remarkably ameliorated the expression of NF‑κB gene after 1, 3 and 24 h exposure to H2 O2 . Conclusions: Findings of the current investigation displayed that pramlintide may act as a protective against oxidative conditions in endothelial cells through modulation of oxidative markers and transcription factor NF‑κB.


Diabetes complications; human umbilical vein endothelial cells; NF‑kappa B; oxidative stress

Full Text:



Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S,

Unwin N, et al. Global and regional diabetes prevalence

estimates for 2019 and projections for 2030 and 2045: Results

from the International Diabetes Federation Diabetes Atlas.

Diabetes Res Clin Pr 2019;157:107843.

Cade WT. Diabetes‑related microvascular and macrovascular

diseases in the physical therapy setting. Phys Ther


Vanessa Fiorentino T, Prioletta A, Zuo P, Folli F.

Hyperglycemia‑induced oxidative stress and its role in diabetes

mellitus related cardiovascular diseases. Curr Pharm Des


Samimi F, Baazm M, Eftekhar E, Rajabi S, Goodarzi MT,

Mashayekhi FJ. Possible antioxidant mechanism of coenzyme

Q10 in diabetes: Impact on Sirt1/Nrf2 signaling pathways. Res

Pharm Sci 2019;14:524‑33.

Williams CR, Lu X, Sutliff RL, Hart CM. Rosiglitazone attenuates NF‑κB‑mediated Nox4 upregulation in hyperglycemia‑activated

endothelial cells. Am J Physiol‑Cell Physiol 2012;303:C213‑23.

Suryavanshi SV, Kulkarni YA. NF‑κβ: A potential target in

the management of vascular complications of diabetes. Front

Pharmacol 2017;8:798.

Edelman S, Maier H, Wilhelm K. Pramlintide in the treatment of

diabetes mellitus. Biodrugs 2008;22:375‑86.

Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L,

Strobel SA, et al. Amylin replacement with pramlintide as an

adjunct to insulin therapy improves long‐term glycaemic and

weight control in Type 1 diabetes mellitus: A 1‑year, randomized

controlled trial. Diabet Med 2004;21:1204‑12.

Ceriello A, Piconi L, Quagliaro L, Wang Y, Schnabel CA,

Ruggles JA, et al. Effects of pramlintide on postprandial glucose

excursions and measures of oxidative stress in patients with

type 1 diabetes. Diabetes Care 2005;28:632‑7.

Ceriello A, Lush CW, Darsow T, Piconi L, Corgnali M,

Nanayakkara N, et al. Pramlintide reduced markers of oxidative

stress in the postprandial period in patients with type 2 diabetes.

Diabetes Metab Res Rev 2008;24:103‑8.

Adler BL, Yarchoan M, Hwang HM, Louneva N, Blair JA,

Palm R, et al. Neuroprotective effects of the amylin analogue

pramlintide on Alzheimer’s disease pathogenesis and cognition.

Neurobiol Aging 2014;35:793‑801.

Akbari V, Zafari S, Yegdaneh A. Anti‑tuberculosis and cytotoxic

evaluation of the seaweed Sargassum boveanum. Res Pharm Sci


Wolf SP. Ferrous ion oxidation in presence of ferric ion indicator

xylenol orange for measurement of hydroperoxides. Methods

Enzymol 1994;233:182‑9.

Mesripour A, Kavianpour M, Hajhashemi V. Antidepressant‑like

effect of minocycline in mice forced swimming test: minor

involvement of the noradrenergic system. Thai J Pharm Sci


Poyner DR. Calcitonin gene‑related peptide: multiple actions,

multiple receptors. Pharmacol Therapeut 1992;56:23‑51.

Brain SD, Grant AD. Vascular actions of calcitonin gene‑related

peptide and adrenomedullin. Physiol Rev 2004;84:903‑34.

Chigurupati S, Kulkarni T, Thomas S, Shah G. Calcitonin

stimulates multiple stages of angiogenesis by directly acting on

endothelial cells. Cancer Res 2005;65:8519‑29.

Tuo Y, Guo X, Zhang X, Wang Z, Zhou J, Xia L, et al. The

biological effects and mechanisms of calcitonin gene‑related

peptide on human endothelial cell. J Recept Sig Transd


Wu X, Song Y, Li S, Liu X, Hua W, Wang K, et al.

Pramlintide regulation of extracellular matrix (ECM) and

apoptosis through mitochondrial‑dependent pathways in

human nucleus pulposus cells. Int J Immunopathol Pharmacol


Yoshimoto T, Gochou N, Fukai N, Sugiyama T, Shichiri M,

Hirata Y. Adrenomedullin inhibits angiotensin II‑induced

oxidative stress and gene expression in rat endothelial cells.

Hypertens Res 2005;28:165‑72.

Martin SD, Caon E, Gabbia D, Zigiotto G, Zhang Z,

Frenguelli L, et al. Investigating the effect of adrenomedullin on

hepatic NF‑κB activation by 2D and 3D hepatic cell cultures.

J Hepatol 2018;68:S134.

Liu Y, Zhang S, Xue J, Wei Z, Ao P, Shen B, et al. CGRP reduces

apoptosis of DRG cells induced by high‑glucose oxidative stress

injury through PI3K/AKT induction of heme oxygenase‑1 and

Nrf‑2 expression. Oxid Med Cell Longev 2019;2019:2053149.