Age dynamics of strain differences in the morphofunctional state of pancreatic beta- and amylin-producing cells in SHR and Wistar rats DOI Creative Commons
T. A. Hrekova, O. V. Melnikova,

Ye. V. Kadzharian

et al.

Current issues in pharmacy and medicine science and practice, Journal Year: 2023, Volume and Issue: 16(3), P. 244 - 248

Published: Nov. 3, 2023

Large-scale epidemiological studies have shown that cardiac pathology and progressive atherosclerosis in patients with diabetes mellitus occurred already at the stage of prediabetes. Obesity insulin resistance affect cardiometabolic health due to pleiotropic effects insulin. Despite vast range research, some aspects remain hidden links overall pathogenesis metabolic hemodynamic disorders. The aim work was study morphofunctional state pancreatic islets (PIs), beta- amylin-producing cells male rats Wistar strain (normotensive) SHR (with spontaneous development hypertension) age dynamics. Materials methods. carried out using 38 SHRs aged 7 24 months. Non-invasive blood pressure (BP) detection procedures were done BP-2000 Blood Pressure Analysis System. PIs examined serial 5-μm thick tissue sections. Beta- detected after histological preprocessing use monoclonal FITC-conjugated antibodies. Image file processing via ImageJ software (National Institutes Health, USA). Levels glycemia monitored a SUPER GLUCOCARD-II glucometer. Results. hyperglycemic both months, 8.41 ± 0.15 mmol/l 8.90 0.14 mmol/l, respectively, elevated BP, 155 5 / 80 mm Hg 165 90 mm, respectively. Old developed PI hypertrophy mainly associated increased number percentage beta-cells, apparently response hyperglycemia. Both adult old SHRs, lower while content amylin higher than those age-matched rats. Conclusions. Male are characterized by persistent increase abnormalities carbohydrate metabolism age, one manifestations which is hyperglycemia worsening age. Chronic requirement finds its expression low this hormone decreased beta-cells animals.

Language: Английский

The relationship between HMGB1 and autophagy in the pathogenesis of diabetes and its complications DOI Creative Commons
Kun‐Lin Yang,

Feng Cao,

Weili Wang

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 29, 2023

Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels and has become the third leading threat to human health after cancer cardiovascular disease. Recent studies have shown that autophagy closely associated with diabetes. Under normal physiological conditions, promotes cellular homeostasis, reduces damage healthy tissues bidirectional effects on regulating However, under pathological unregulated activation leads cell death may contribute progression of Therefore, restoring be key strategy treat High-mobility group box 1 protein (HMGB1) chromatin mainly present in nucleus can actively secreted or passively released from necrotic, apoptotic, inflammatory cells. HMGB1 induce activating various pathways. Studies plays an important role insulin resistance In this review, we will introduce biological structural characteristics summarize existing knowledge relationship between HMGB1, autophagy, diabetes, diabetic complications. We also potential therapeutic strategies useful for prevention treatment diabetes its

Language: Английский

Citations

24
Intercommunication between metal ions and amyloidogenic peptides or proteins in protein misfolding disorders DOI
Jong‐Min Suh, Mingeun Kim,

Jeasang Yoo

et al.

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 478, P. 214978 - 214978

Published: Dec. 16, 2022

Language: Английский

Citations

32
Protein misfolding and related human diseases: A comprehensive review of toxicity, proteins involved, and current therapeutic strategies DOI
Asra Nasir Khan, Rizwan Hasan Khan

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 223, P. 143 - 160

Published: Nov. 8, 2022

Language: Английский

Citations

31
Zinc and iron dynamics in human islet amyloid polypeptide-induced diabetes mouse model DOI Creative Commons
Ayako Fukunaka,

Mari Shimura,

Takayuki Ichinose

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 15, 2023

Abstract Metal homeostasis is tightly regulated in cells and organisms, its disturbance frequently observed some diseases such as neurodegenerative metabolic disorders. Previous studies suggest that zinc iron are necessary for the normal functions of pancreatic β cells. However, distribution elements conditions pathophysiological significance dysregulated islet diabetic have remained unclear. In this study, to investigate dynamics islets a mouse model expressing human amyloid polypeptide (hIAPP): hIAPP transgenic (hIAPP-Tg) mice, we performed imaging analysis using synchrotron scanning X-ray fluorescence microscopy quantitative inductively coupled plasma mass spectrometry. We found islets, significantly decreased early stage diabetes, while gradually concurrently with increase blood glucose levels hIAPP-Tg mice. Notably, when and/or were dysregulation glucose-stimulated mitochondrial respiration was observed. Our findings may contribute clarifying roles under conditions.

Language: Английский

Citations

9
Bovine serum albumin uptake and polypeptide disaggregation studies of hypoglycemic ruthenium(II) uracil Schiff-base complexes DOI Creative Commons

Daniel M. Makanyane,

Sanam Maikoo,

Fanie R. van Heerden

et al.

Journal of Inorganic Biochemistry, Journal Year: 2024, Volume and Issue: 255, P. 112541 - 112541

Published: March 27, 2024

Our prior studies have illustrated that the uracil ruthenium(II) diimino complex, [Ru(H

Language: Английский

Citations

3
The protective effect of amylin in type 2 diabetes: Yes or no DOI Creative Commons
Mohammad Saud Alanazi, Hayder M. Al‐kuraishy,

Ali K. Albuhadily

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177593 - 177593

Published: April 1, 2025

Language: Английский

Citations

0
Bridging Pancreatic Amyloidosis and Neurodegeneration: The Emerging Role of Amylin in Diabetic Dementia DOI Open Access
Gourav Shome, Ritwick Mondal, Shramana Deb

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(11), P. 5021 - 5021

Published: May 23, 2025

A hallmark of type 2 diabetes mellitus (T2DM) is the presence abundant amyloid deposits composed polypeptide (amylin) within pancreatic islets Langerhans. Given its high prevalence among diabetic individuals, human amylin fibrillization has long been considered a key pathogenic factor in T2DM. Co-secreted with insulin, can misfold and aggregate, inducing β-cell toxicity, impairing insulin secretion, accelerating disease progression. Emerging evidence also indicates that accumulates brains patients Alzheimer’s disease, where it may interact amyloid-β (Aβ) to promote neurodegeneration. Although underlying mechanisms remain under investigation, aggregates have shown disrupt mitochondrial function, trigger endoplasmic reticulum stress, activate NLRP3 inflammasome. Additionally, T2DM-associated cerebrovascular alterations compound cognitive decline. This review, based on comprehensive literature search across major biomedical databases up January 2025, synthesizes current as molecular link between metabolic neurodegenerative disorders. We highlight aggregation potential early marker dementia risk T2DM examine relationship proteostasis-associated proteins. Finally, we discuss emerging diagnostic therapeutic strategies targeting pathology, offering new perspectives preventing or delaying neurodegeneration individuals

Language: Английский

Citations

0
Natural compound plumbagin based inhibition of hIAPP revealed by Markov state models based on MD data along with experimental validations DOI
Faisal Nabi, Owais Ahmad,

Adeeba Khan

et al.

Proteins Structure Function and Bioinformatics, Journal Year: 2024, Volume and Issue: 92(9), P. 1070 - 1084

Published: March 18, 2024

Abstract Human islet amyloid polypeptide (amylin or hIAPP) is a 37 residue hormone co‐secreted with insulin from β cells of the pancreas. In patients suffering type‐2 diabetes, amylin self‐assembles into fibrils, ultimately leading to death pancreatic cells. However, research gap exists in preventing and treating such amyloidosis. Plumbagin, natural compound, has previously been demonstrated have inhibitory potential against Our investigation unveils collapsible regions within hIAPP that, upon collapse, facilitates hydrophobic pi‐pi interactions, aggregation. Intriguingly plumbagin exhibits ability bind these specific regions, thereby impeding aforementioned interactions that would otherwise drive We used atomistic molecular dynamics approach determine secondary structural changes. MSM shows metastable states forming native like structure presence PGN. silico results concur vitro results. The ThT assay revealed striking 50% decrease fluorescence intensity at 1:1 ratio Plumbagin. This finding suggests significant inhibition fibril formation by plumbagin, as directly correlates fibrils. Further TEM images disappearance fibrils pre‐treated samples. Also, we shown disrupts intermolecular hydrogen bonding an increase average beta strand spacing, causing disaggregation pre‐formed demonstrating overall disruption aggregation machinery hIAPP. work first report detailed simulation 22 μs for Overall, our studies put candidate both preventive therapeutic

Language: Английский

Citations

3
Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus DOI Creative Commons

Adriana Sevcuka,

Kenneth White, Cassandra Terry

et al.

Life, Journal Year: 2022, Volume and Issue: 12(4), P. 583 - 583

Published: April 14, 2022

Cases of Type 2 Diabetes Mellitus (T2DM) are increasing at an alarming rate due to the rise in obesity, sedentary lifestyles, glucose-rich diets and other factors. Numerous studies have increasingly illustrated pivotal role that human islet amyloid polypeptide (hIAPP) plays pathology T2DM through damage subsequent loss pancreatic β-cell mass. HIAPP can misfold form fibrils which preceded by pre-fibrillar oligomers monomers, all been linked, a certain extent, cytotoxicity range proposed mechanisms. This review provides up-to-date summary recent progress field, highlighting factors contribute hIAPP misfolding aggregation such as protein concentration, cell stress, molecular chaperones, immune system response cross-seeding with amyloidogenic proteins. Understanding structure how these affect formation will help us better understand misfolds aggregates and, importantly, identify potential therapeutic targets for inhibiting amyloidosis so alternate more effective treatments be developed.

Language: Английский

Citations

12
Big versus small: The impact of aggregate size in disease DOI Creative Commons
Brianna Hnath, Jiaxing Chen, Joshua Reynolds

et al.

Protein Science, Journal Year: 2023, Volume and Issue: 32(7)

Published: May 27, 2023

Protein aggregation results in an array of different size soluble oligomers and larger insoluble fibrils. Insoluble fibrils were originally thought to cause neuronal cell deaths neurodegenerative diseases due their prevalence tissue samples disease models. Despite recent studies demonstrating the toxicity associated with oligomers, many therapeutic strategies still focus on or consider all types aggregates as one group. Oligomers require modeling strategies, targeting toxic species is crucial for successful study development. Here, we review role different-size disease, how factors contributing (mutations, metals, post-translational modifications, lipid interactions) may promote opposed We two computational (molecular dynamics kinetic modeling) they are used model both Finally, outline current aggregating proteins strengths weaknesses versus Altogether, aim highlight importance distinguishing difference between determining which when creating therapeutics protein disease.

Language: Английский

Citations

7