Pankreasregeneration nach Teilresektion beim Menschen

Menge, BA; Tannapfel, Andrea; Belyaev, Orlin; Drescher, Robert; Müller, C.; Uhl, Waldemar; Schmidt, Wolfgang E.; Meier, Juris J.

doi:10.1055/s-0028-1089538

Cited by 1 publication

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“…Beta cells in rodent models of diabetes retain a capacity for beta cell replication and typically have a high rate of beta cell apoptosis (Moffett et al, 2015;Hao et al, 2017). In contrast, beta cells in adult humans have minimal capacity for beta cell replication (Butler et al, 2007;Menge et al, 2008;Gregg et al, 2012;Dai et al, 2017). Also, in the setting of misfolded protein stress or other toxicity, beta cells in humans have a low frequency of apoptosis due to upregulation of potent pro-survival signaling at the expense of beta cell function (Montemurro et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of IAPP suppression in mouse and human islets by GLP-1 analogue conjugated antisense oligonucleotide

Gurlo

Prakash²,

Wang³

et al. 2023

Front. Mol. Biosci.

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Insulin resistance is the major risk factor for Type 2 diabetes (T2D). In vulnerable individuals, insulin resistance induces a progressive loss of insulin secretion with islet pathology revealing a partial deficit of beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP). IAPP is co-expressed and secreted with insulin by beta cells, expression of both proteins being upregulated in response to insulin resistance. If IAPP expression exceeds the threshold for clearance of misfolded proteins, beta cell failure occurs exacerbated by the action of IAPP toxicity to compromise the autophagy lysosomal pathway. We postulated that suppression of IAPP expression by an IAPP antisense oligonucleotide delivered to beta cells by the GLP-1 agonist exenatide (eGLP1-IAPP-ASO) is a potential disease modifying therapy for T2D. While eGLP1-IAPP-ASO suppressed mouse IAPP and transgenic human IAPP expression in mouse islets, it had no discernable effects on IAPP expression in human islets under the conditions studied. Suppression of transgenic human IAPP expression in mouse islets attenuated disruption of the autophagy lysosomal pathway in beta cells, supporting the potential of this strategy.

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