Insulin Structure and Stability

Brange, Jens; Langkjoer, L

doi:10.1007/978-1-4899-1236-7_11

Cited by 238 publications

(213 citation statements)

References 80 publications

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“…It consists of two polypeptidic chains connected by two disulfur bridges: the A chain of 21 amino acids and the B chain of 30 amino acids. [24] The insulin monomer is a wedgeshaped molecule with a size of about 2 × 2.5 × 2 nm. Insulin is known to form multimers: the dimer has an oblong shape of approximately 2 × 2.5 × 4 nm, and the hexamer is a flattened spheroid with a diameter of about 5 nm and a height of about 3 nm.…”

Section: Proteinsmentioning

confidence: 99%

Surface composition of insulin and albumin adsorbed on polymer substrates as revealed by multivariate analysis of ToF‐SIMS data

Henry

Bertrand

2008

Surface & Interface Analysis

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The structure and the composition of adsorbed protein films containing human serum albumin (HSA) and/or human insulin were studied with time-of-flight secondary ion mass spectrometry (ToF-SIMS). The proteins were adsorbed either on native polycarbonate (PC) membranes or on PC membranes treated with poly(N-vinylpyrrolidone) (PVP/PC). These membranes have been developed for their use as encapsulation membranes in a bioartificial pancreas. Principal component analysis (PCA) of the ToF-SIMS results allowed the determination of the main factors affecting the surface structure and composition of the protein layer. The substrate surface properties were found to be the most influencing factor. The amount and type of the adsorbed protein also influence the adsorbed protein layer surface composition and structure. A partial least squares (PLS) regression model allowed confirmation of the correlation between the adsorbed amount of protein and the surface composition of the protein layer.

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Section: Proteinsmentioning

confidence: 99%

Surface composition of insulin and albumin adsorbed on polymer substrates as revealed by multivariate analysis of ToF‐SIMS data

Henry

Bertrand

2008

Surface & Interface Analysis

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“…Treatment with an anti-insulin antibody decreases Akt phosphorylation and human islet survival Since insulin is secreted by beta cells, is a strong activator of Akt [26] and is heat-sensitive [27], we examined whether insulin was the factor responsible for the observed rise in Akt phosphorylation. Using an insulin ELISA, we found that after 24 h, isletconditioned medium contained significantly elevated levels of insulin (conditioned medium 59.2±9.6 mU/ml; fresh medium 1.08±0.062 μU/ml) (Fig.…”

Section: Regular Medium Replacement Decreases Akt Phosphorylationmentioning

confidence: 99%

Autocrine insulin action activates Akt and increases survival of isolated human islets

et al. 2006

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Aims/hypothesis The phosphatidylinositol 3-kinase (PI3K)/ Akt pathway plays a critical role in promoting the survival of pancreatic beta cells. Akt becomes activated in isolated human islets following overnight culture despite significant levels of cell death. The aim of the current study was to identify the cause of the observed increase in Akt phosphorylation in isolated islets. We hypothesised that a factor secreted by the islets in culture was acting in an autocrine manner to activate Akt. Methods In order to identify the stimulus of the PI3K/Akt pathway in culture, we examined the effects of different culture conditions on Akt phosphorylation and islet survival during the immediate post-isolation period. Results We demonstrated that islet-conditioned medium induced Akt phosphorylation in freshly isolated human islets, whereas frequent medium replacement decreased Akt phosphorylation. Following overnight culture, islet-conditioned medium contained significantly elevated levels of insulin, indicating that insulin may be responsible for the observed increase in Akt phosphorylation. Indeed, treatment with an anti-insulin antibody or with inhibitors of insulin receptor/IGF receptor 1 kinase activity suppressed Akt phosphorylation, leading to decreased islet survival. In addition, dispersion of islets into single cells also suppressed Akt phosphorylation and induced islet cell death, indicating that islet integrity is also required for maximal Akt phosphorylation. Conclusions/interpretation Our findings demonstrate that insulin acts in an autocrine manner to activate Akt and mediate the survival of isolated human islets. These findings provide new information on how culturing islets prior to transplantation may be beneficial to their survival by allowing for autocrine activation of the pro-survival Akt pathway.

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“…For some, the physiologic function is known and the three-dimensional structure of the native state has been determined [4][5][6][7][8][9][10][11]. However, in each amyloidosis, the pathologic lesions characterizing the disease comprise mainly aggregates of the respective protein.…”

Section: Introductionmentioning

confidence: 99%