Regulation of the assembly and amyloid aggregation of murine amylin by zinc

Erthal, Luiza C. S.; Marques, Adriana Aparecida; Almeida, Fábio C. L.; Melo, Gustavo Mendes de; Carvalho, Camila Miranda de; Palmieri, L.C.; Cabral, Katia M. S.; Fontes, Giselle N.; Lima, L.M.T.R.

doi:10.1016/j.bpc.2016.09.008

Cited by 37 publications

(39 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, both pramlintide and rat IAPP give rise to oligomerics pecies and fibrils [16] also without other compounds in vitro. [17] These aggregates show morphologic [18,19] and pH-dependence features similart ot hose of h-IAPP, [20] but of minor importance.A lthough many transgenic modelsh aveb een developedt oo verexpressh uman IAPP, [21][22][23] the toxicityo fb-cell caused by IAPP remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Zinc Interactions with a Soluble Mutated Rat Amylin to Mimic Whole Human Amylin: An Experimental and Simulation Approach to Understand Stoichiometry, Speciation and Coordination of the Metal Complexes

Magrı̀

Tabbı̀

Natale

et al. 2020

Chemistry A European J

View full text Add to dashboard Cite

Islet amyloid polypeptide (IAPP) is ah ormone cosecreted with insulin and zinc from pancreatic b-cells. To overcome the low solubility of human IAPP,wecharacterized zinc complexes speciesf ormed with 1) am utated form of rat-IAPP(1-37;R18 H) able to mimic the human IAPP,2)the r-IAPP(1-37)a nd the IAPP(1-8) fragment. Stoichiometry,s peciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometry and NMR measurements combined with DFT and free-energy simulations. Mononu-clear species startt of orma round pH 6; Zn 2 + binds both His18 and N-aminot erminus in rat-IAPP(1-37;R 18 H). The in silico study allows us to assess not only as tructured turn compactd omain in r-IAPP(1-37) and r-IAPP(1-37;R 18 H) featured by ad ifferent free energyb arrierf or the transition from the compactt oe longated conformation upon the coordination of Zn 2 + ,b ut also to bring into light ac oordination shell further stabilizedb ynoncovalent interactions.

show abstract

Section: Introductionmentioning

confidence: 99%

Zinc Interactions with a Soluble Mutated Rat Amylin to Mimic Whole Human Amylin: An Experimental and Simulation Approach to Understand Stoichiometry, Speciation and Coordination of the Metal Complexes

Magrı̀

Tabbı̀

Natale

et al. 2020

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…These limitation stimulated the use of transgenic rodents [68–70]. We have previously reported the in vitro amyloid nature of murine amylin [38,39], and subsequently the toxic nature of murine amylin oligomers and its presence in pancreatic tissue in natural abundance of wild-type mice [41]. The techniques used along the years for identification of oligomeric and fibers forms has been demonstrated to have certain limitations [39,71].…”

Section: Discussionmentioning

confidence: 99%

“…It is known that human amylin forms amyloid fibrils [36,37], but the aggregation of murine variant still under discussion. Our group demonstrated that murine amylin and amylin analogue pramlintide can aggregate in vitro [38–40]. Toxic oligomers in pancreatic islets can be found in non-transgenic mice [41].…”

Section: Introductionmentioning

confidence: 99%

“…Zinc has been described as a partner in amylin oligomerization and fibrillation, both human [44–47] and murine [38] The zinc content on β-pancreatic granule has been shown to be reduced in diabetic patients (Sjögren et al 1988) compared to healthy individuals [49], which rise the hypothesis of the role of pancreatic zinc in triggering the instability of amylin in vivo .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Zinc restriction promotes β-cell hyper-hormonemia and endocrine pancreas degeneration in mice

Sisnande

Lima

Silva

et al. 2019

Preprint

View full text Add to dashboard Cite

Zinc is a key component of proteins, including interaction with varying pancreatic hormones, including insulin and amylin. Zinc is key in insulin crystallinity in ZnT8 knock-out mice models, although the dietary role of zinc restriction over both energetic metabolism and ß-pancreatic hormonemia and morphology remained unexplored. We aimed to test whether dietary zinc restriction on swiss male mice would impact over endocrine pancreas and metabolic phenotype. We evaluated the role of dietary zinc restriction on ß-pancreatic hormonemia on non-transgenic Swiss male mice weaned onto a control or low-zinc diet for 4 weeks. Growth, glycemia, insulinemia, amylinemia and pancreatic islet were smaller in intervention group despite insulin crystallinity in secretory granules. We have found overlabelling for insulin, amylin and toxic oligomers in apoptotic pancreatic islet. High production of β-pancreatic hormones in zinc-restricted animals counteract the decreasing islet size due to their apoptotic cells. We conclude that zinc deficiency is sufficient to promote islet β-cell hormonal disruption and degeneration.

show abstract

“…Aggregation of amylin was discovered to be minimized in proline-rich variants (14), which inspired the design of the triple-proline human amylin analogue named pramlintide (Pro 25,28,29 ; CAS #151126-32-8; acetate salt CAS #196078-30-5; patent US 5,998,367 (15)). Although proline-rich variants such as murine amylin and pramlintide still holds amylodogenic features (16)(17)(18), they show improved physico-chemical properties and similar pharmacologic properties of human amylin (19) resulting in its approval by the FDA in 2004 and entering the US market as first-in-class in 2005 (20). Other approaches have been developed aimed to overcome the stability problem of amylin analogues, such as PEGylation ( (21,22) patent US 20,160,331,811) and molecular confinement into liposomes (23) or polymeric particles (21).…”

Section: Introductionmentioning

confidence: 99%

Physico-chemical properties of co-formulation of insulin with pramlintide

Silva

Lima

2017

Preprint

View full text Add to dashboard Cite

Since the discovery of amylin its use has been discouraged by the inadequacy of the protocol involving multiple injections in addition to insulin. While a combined fixed-dose formulation is thus highly desirable, it has long been limited due to incompatibility as historically documented. We have investigated the compatibility of regular and fast-acting insulin analogues (Aspart, AspB28, and LisPro, LysB28ProB29) with the amylin analogue pramlintide. Insulin interacts with pramlintide, forming heterodimers as probed by electrospray ionization - ion mobility spectrometry-mass spectrometry. While their interaction is likely to delay the amyloid aggregation of pramlintide in phosphate-buffered solution pH 7.0, they do not prevent aggregation at this condition. At acidic sodium acetate solution pH 5.0, combination of pramlintide and the fast-acting insulin analogues become stable against amyloid aggregation. The co-formulated product at high concentration of both pramlintide (600 μg/mL,150 μM) and LisPro insulin (50 IU/mL, 300 μM) showed also stability against amyloid aggregation. These data indicate a potential for the development of a co-formulation of fast-acting LisPro insulin with pramlintide, which could bring benefits for the combined therapy.AbbreviationsIAPP,islet amyloid polypeptide;ESI-IMS-MS,Electrospray Ionization–Ion Mobility Spectrometry–Mass Spectrometry.

show abstract

Regulation of the assembly and amyloid aggregation of murine amylin by zinc

Cited by 37 publications

References 112 publications

Zinc Interactions with a Soluble Mutated Rat Amylin to Mimic Whole Human Amylin: An Experimental and Simulation Approach to Understand Stoichiometry, Speciation and Coordination of the Metal Complexes

Zinc Interactions with a Soluble Mutated Rat Amylin to Mimic Whole Human Amylin: An Experimental and Simulation Approach to Understand Stoichiometry, Speciation and Coordination of the Metal Complexes

Zinc restriction promotes β-cell hyper-hormonemia and endocrine pancreas degeneration in mice

Physico-chemical properties of co-formulation of insulin with pramlintide

Contact Info

Product

Resources

About