Interaction of esomeprazole with insulin detemir and human albumin: A potential cause of hypoglycemia

Hamdan, Imad I.; Farah, Dua'a G.; Khalil, Enam A.; Mansour, Randa S.H.; Abdel-Halim, Heba

doi:10.1016/j.bpc.2022.106809

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…In our case, the turbidity‐based measurement showed that at pH 2.0 and 65 °C temperature, native insulin under continuous agitation over a period of 24 h forms insulin fibrils that increases the turbidity of the solution. [ 45 ] Figure 2C showed that the formation of IF results in a very significant increase in the absorbance value at 350 nm. However, in the presence of LABC‐2 and DHLABC‐2 polymers, the absorbance values reduced to ≈72% and ≈86% respectively, indicating their potent anti‐fibrillating efficacies with DHLABC‐2 polymer showing better inhibition ability.…”

Section: Resultsmentioning

confidence: 99%

Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation

Bera

Ghosh

et al. 2023

Macromolecular Bioscience

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Lipoic acid (LA) and dihydrolipoic acid (DHLA) are well established antioxidants to scavenge reactive oxygen species (ROS). However, they are carboxylates with ≈4.7 pKa making them negatively charged at physiological pH (7.4) reducing their passive diffusion through cell membranes. LA is known to be capable of reducing protein fibrillation. Incorporation of LA and especially DHLA in polymer side chains are scarce. Herein, the first examples of the anti‐amyloidogenic effect of LA and DHLA incorporated into the side‐chain of a block copolymer with a water‐soluble poly(polyethylene glycol methyl ether methacrylate) (PPEGMA) segment are presented. The resultant polymers show improved ROS scavenging activity and improved ability to reduce insulin fibrillation compared to free LA and DHLA. Furthermore, the resultant polymers are also capable of disintegrating preformed insulin firbrils. Interestingly, polymers with dihydro‐lipoate moieties showed 93% free radical scavenging activity with 91% anti‐fibrillating efficacies for insulin protein confirmed by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay and Thioflavin T (ThT) dye binding study, respectively. Further, the antioxidant polymers increase the cell viability against fibrillar insulin aggregates that may be involved in the etiology of several diseases. Overall, this work reveals that antioxidant polymer‐based therapeutic agents can serve as a powerful modulation strategy for developing novel drugs in future against amyloid‐related disorders.

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Section: Resultsmentioning

confidence: 99%

Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation

Bera

Ghosh

et al. 2023

Macromolecular Bioscience

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“…[13][14][15] Insulin also fibrillates during industrial production, transportation, and storage which presents significant challenges during its phar-maceutical use. [16][17][18][19][20] This has necessitated the identification of small molecules to detect and prevent insulin aggregation.…”

Section: Introductionmentioning

confidence: 99%

Dual Role of a Fluorescent Small Molecule as a Sensor and Inhibitor of Protein Fibrillation

Das

Sah

Saraogi

2023

Chemistry An Asian Journal

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Ordered fibrillar aggregates of proteins, called amyloids, are prevalent in several diseases like Alzheimer's, Parkinson's, and Type II diabetes. The key challenge in the treatment of such diseases is the early detection of protein fibrillation and its effective inhibition using extrinsic agents. Thus, molecules that can both detect and inhibit protein fibril formation have great diagnostic and therapeutic utility. Using insulin as a model protein, we report the dual action of an isoquinoline based molecule, named MK14 which detects and prevents insulin fibrillation. Dose dependent inhibition of insulin fibrillation by MK14 gave an IC50 value of 9 μM, and mechanistic investigations suggested that MK14 prevented the elongation of fibrils by interacting with pre‐fibrillar intermediates. The fluorescence of MK14 enhanced upon binding to fibrils of insulin as well as those of α‐synuclein, the protein involved in Parkinson's disease. MK14 is an environmentally sensitive fluorophore, which could also detect amorphous aggregates of insulin. The dual nature of MK14 as an inhibitor and detector of protein fibrillation makes it an attractive lead compound for monitoring and disrupting protein amyloidogenesis.

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“…The unique mechanism of this covalently modified insulin analog relies on its reversible binding to human albumin through the fatty acid extension [6,11]. This albumin bound form of insulin serves as a reservoir that continually and slowly releases detemir insulin into the bloodstream and delays the hormone's action [6,11,12] (Figure S2). Detemir has demonstrated greater efficacy and reproducible absorption rate compared to neutral protamine hagedorn (NPH) insulin and insulin glargine [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Comparative Study of High-Resolution LysB29(Nε-myristoyl) des(B30) Insulin Structures Display Novel Dynamic Causal Interrelations in Monomeric-Dimeric Motions

et al. 2023

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The treatment of insulin-dependent diabetes mellitus is characterized by artificial supplementation of pancreatic β-cell ability to regulate sugar levels in the blood. Even though various insulin analogs are crucial for reasonable glycemic control, understanding the dynamic mechanism of the insulin analogs may help to improve the best-protracted insulin analog to assist people with type 1 diabetes (T1D) to live comfortably while maintaining tight glycemic control. Here, we present the high-resolution crystal structure of NN304, known as insulin detemir, to 1.7 Å resolution at cryogenic temperature. We computationally further investigated our crystal structure’s monomeric-dimeric conformation and dynamic profile by comparing it with a previously available detemir structure (PDB ID: 1XDA). Our structure (PDB ID: 8HGZ), obtained at elevated pH, provides electrostatically triggered minor movements in the equilibrium between alternate conformational substates compared to the previous structure, suggesting it might induce an intermediate state in the dissociation pathway of the insulin detemir’s hexamer:dihexamer equilibrium. Supplemented with orientational cross-correlation analysis by a Gaussian network model (GNM), this alternate oligomeric conformation offers the distinct cooperative motions originated by loose coupling of distant conformational substates of a protracted insulin analog that has not been previously observed.

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Interaction of esomeprazole with insulin detemir and human albumin: A potential cause of hypoglycemia

Cited by 6 publications

References 35 publications

Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation

Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation

Dual Role of a Fluorescent Small Molecule as a Sensor and Inhibitor of Protein Fibrillation

Comparative Study of High-Resolution LysB29(Nε-myristoyl) des(B30) Insulin Structures Display Novel Dynamic Causal Interrelations in Monomeric-Dimeric Motions

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