Inhibition of Insulin Degrading Enzyme to Control Diabetes Mellitus and its Applications on some Other Chronic Disease: a Critical Review

Azam, Md. Shofiul; Wahiduzzaman, Md; Reyad‐ul‐Ferdous, Md.; Islam, Md. Nahidul; Roy, Mukta

doi:10.1007/s11095-022-03237-7

Cited by 12 publications

(4 citation statements)

References 102 publications

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“…Moreover, all compounds, except for compounds 9 and 13 , showed insulysin inhibitor values between Pa = 0.515 to Pa = 0.729, indicating that these compounds could potentially be therapeutic agents for diabetes treatment. Using a clearance mechanism anchored on degradation, IDE controls the amount of circulating insulin in several organs 69 , 70 . The reference drug shows no activity as an insulysin inhibitor.…”

Section: Resultsmentioning

confidence: 99%

Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods

Saif,

Esha,

Quayum

et al. 2024

Sci Rep

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In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1–16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone’s C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO–LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of − 8.5 kcal mol−1. This result outperformed the affinity of the reference standard dapagliflozin (− 7.9 kcal mol−1) as well as two other compounds that target human IDE, namely vitexin (− 8.3 kcal mol−1) and myricetin (− 8.4 kcal mol−1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein–ligand complex at the active site.

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Section: Resultsmentioning

confidence: 99%

Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods

Saif,

Esha,

Quayum

et al. 2024

Sci Rep

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“…IDE (Insulin Degrading Enzyme) is responsible for degrading both insulin and Aß-peptides. Dysfunctional IDE activity leads to impaired insulin signaling in T2MD and accumulation of Aß-peptides in AD (Tian et al, 2023;Azam et al, 2022;Hong et al, 2008).…”

Section: Common Genes Involved In Both Diseasesmentioning

confidence: 99%

Alzheimer’s Disease and Type 2 Diabetes Relationships. I. Cellular and Molecular Common Pathological Mechanisms

Rodríguez-Casado,

Álvarez,

Toledano-Díaz

et al. 2024

Preprint

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Type 2 Diabetes Mellitus and Alzheimer's disease are two diseases with a high incidence today that share similar pathophysiological mechanisms suggesting a potential causal relationship between them. In fact, Alzheimer-associated Mellitus Diabetes is also known as Type 3 Diabetes Mellitus and constitutes a diabetes intricately linked to Alzheimer's disease. Central to this association is insulin resistance, a key factor leading to decreased insulin sensitivity, hyperglycemia, and impaired glucose uptake. Because of this, the brain is altered resulting in energy deficits and neuronal damage associated with neurodegenerative disorder characteristic of Alzheimer's disease. Both diseases exhibit common biochemical and physiological characteristics such as inflammation, mitochondrial dysfunction, oxidative stress, and the formation of advanced glycation end products. Understanding the complex pathophysiology of Type 3 Mellitus Diabetes and identifying common features shared with Diabetes and Alzheimer's disease are essential steps towards potential therapeutic interventions targeting the insulin resistance pathway. The authors of this review on the relationships between type 2 diabetes and Alzheimer's disease have developed two works. In the first (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. I. Common pathogenic mechanisms), authors explore the shared (physiological, genetics and molecular) pathological changes occurring in Type 2 Mellitus Diabetes and Alzheimer's disease as well as pathways such as AMPK, PPARγ, cAMP, and PI3K/Akt as potential targets for managing Type 3 Diabetes Mellitus. By exploring these intricate mechanisms, the goal is to uncover their interdependencies and facilitate the discovery of innovative pharmacological and nutritional (epigenetics) strategies. In the second paper (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. II Potential therapies) we describe possible nutritional intervention, particularly dietary patterns and phytochemicals that can enhance the effects of pharmaceutical drugs designed against pathological mechanisms involved in the complex dual disease Type 2 Diabetes Mellitus and Alzheimer's disease (or in Type 3 Diabetes Mellitus as other authors consider).

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“…In addition, insulin-degrading enzyme (IDE) causes degradation of Aβ in both in vitro and in vivo models [ 36 - 38 ]. Qiu et al (1998) and Vekrellis et al (2000) have suggested that insulin influences IDE in the clearance of Aβ in AD patients [ 39 , 40 ].…”

Section: Hyperglycaemia and Admentioning

confidence: 99%

Linking Diabetes to Alzheimer’s Disease: Potential Roles of Glucose Metabolism and Alpha-Glucosidase

Khaw

Yoon

Wee

et al. 2023

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Alzheimer’s disease (AD) and type 2 diabetes mellitus (DM) are more prevalent with age- ing and cause a substantial global socio-economic burden. The biology of these two conditions is well elaborated, but whether AD and type 2 DM arise from coincidental roots in ageing or are linked by pathophysiological mechanisms remains unclear. Research findings involving animal models have identified mechanisms shared by both AD and type 2 DM. Deposition of β-amyloid peptides and for- mation of intracellular neurofibrillary tangles are pathological hallmarks of AD. Type 2 DM, on the other hand, is a metabolic disorder characterised by hyperglycaemia and insulin resistance. Several studies show that improving type 2 DM can delay or prevent the development of AD, and hence, pre- vention and control of type 2 DM may reduce the risk of AD later in life. Alpha-glucosidase is an en- zyme that is commonly associated with hyperglycaemia in type 2 DM. However, it is uncertain if this enzyme may play a role in the progression of AD. This review explores the experimental evidence that depicts the relationship between dysregulation of glucose metabolism and AD. We also delineate the links between alpha-glucosidase and AD and the potential role of alpha-glucosidase inhibitors in treat- ing AD.

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Inhibition of Insulin Degrading Enzyme to Control Diabetes Mellitus and its Applications on some Other Chronic Disease: a Critical Review

Cited by 12 publications

References 102 publications

Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods

Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods

Alzheimer’s Disease and Type 2 Diabetes Relationships. I. Cellular and Molecular Common Pathological Mechanisms

Linking Diabetes to Alzheimer’s Disease: Potential Roles of Glucose Metabolism and Alpha-Glucosidase

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