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Insulin AND amyloid

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https://www.readbyqxmd.com/read/28928089/in-vitro-and-in-vivo-studies-supporting-the-therapeutic-potential-of-zp3022-in-diabetes
#1
Jolanta Skarbaliene, Kristoffer T Rigbolt, Keld Fosgerau, Nils Billestrup
GLP-1-gastrin dual agonist ZP3022 has been shown to increase β-cell mass with a concomitant improvement of glycemic control in diabetic mice and rats. Here we tested the in-vitro effects of ZP3022 on β-cell proliferation, islet apoptosis and glucose-stimulated insulin secretion (GSIS) in rat islets of Langerhans. Moreover, gene expression profiling in whole pancreas from Zucker Diabetic Fatty (ZDF) rats was performed to characterize genes differently regulated by short-term treatment with ZP3022. Treatments with exendin-4, gastrin-17 alone or in combination were included in the studies...
September 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28918138/characterizing-effects-of-feed-restriction-and-glucagon-like-peptide-2-administration-on-biomarkers-of-inflammation-and-intestinal-morphology
#2
S K Kvidera, E A Horst, M V Sanz Fernandez, M Abuajamieh, S Ganesan, P J Gorden, H B Green, K M Schoenberg, W E Trout, A F Keating, L H Baumgard
Inadequate feed consumption reduces intestinal barrier function in both ruminants and monogastrics. Objectives were to characterize how progressive feed restriction (FR) affects inflammation, metabolism, and intestinal morphology, and to investigate if glucagon-like peptide 2 (GLP2) administration influences the aforementioned responses. Twenty-eight Holstein cows (157 ± 9 d in milk) were enrolled in 2 experimental periods. Period 1 [5 d of ad libitum (AL) feed intake] served as baseline for period 2 (5 d), during which cows received 1 of 6 treatments: (1) 100% of AL feed intake (AL100; n = 3), (2) 80% of AL feed intake (n = 5), (3) 60% of AL feed intake (n = 5), (4) 40% of AL feed intake (AL40; n = 5), (5) 40% of AL feed intake + GLP2 administration (AL40G; 75 µg/kg of BW s...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28917147/combined-in-silico-approaches-for-the-identification-of-novel-inhibitors-of-human-islet-amyloid-polypeptide-hiapp-fibrillation
#3
Palak Patel, Krupali Parmar, Vivek K Vyas, Dhaval Patel, Mili Das
Human islet amyloid polypeptide (hIAPP) is a natively unfolded polypeptide hormone of glucose metabolism, which is co-secreted with insulin by the β-cells of the pancreas. In patients with type 2 diabetes, IAPP forms amyloid fibrils because of diabetes-associated β-cells dysfunction and increasing fibrillation, in turn, lead to failure of secretory function of β-cells. This provides a target for the discovery of small organic molecules against protein aggregation diseases. However, the binding mechanism of these molecules with monomers, oligomers and fibrils to inhibit fibrillation is still an open question...
September 6, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28905065/be-positive-optimizing-pramlintide-from-microcanonical-analysis-of-amylin-isoforms
#4
Rafael B Frigori
Amylin, or human islet amyloid polypeptide (hIAPP), is a 37-residue hormone synergistic to insulin and co-secreted with it by β-cells in the pancreas. The deposition of its cytotoxic amyloid fibrils is strongly related to the progression of Type II diabetes (T2D) and islet graft failures. Notably, isoforms from some mammalian species, such as rats (rIAPP) and porcine (pIAPP), present a few key mutations preventing aggregation. This has lead to biotechnological development of drugs for adjunct therapies of T2D, such as pramlintide, a variant of hIAPP inspired by rIAPP whose proline substitutions have β-strand fibril-breaking properties...
September 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28900141/dianxianning-improved-amyloid-%C3%AE-induced-pathological-characteristics-partially-through-daf-2-daf-16-insulin-like-pathway-in-transgenic-c-elegans
#5
Dejuan Zhi, Dong Wang, Wenqi Yang, Ziyun Duan, Shuqian Zhu, Juan Dong, Na Wang, Ningbo Wang, Dongqing Fei, Zhanxin Zhang, Xin Wang, Meizhu Wang, Hongyu Li
Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ1-42 C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899812/the-starving-brain-overfed-meets-undernourished-in-the-pathology-of-mild-cognitive-impairment-mci-and-alzheimer-s-disease-ad
#6
REVIEW
Kelly J Gibas
Type II Diabetes affects 400 million people worldwide (IDF, 2013). The pathology is paradoxical: internal starvation activated by overfeeding. Hyperinsulinemic impairments of glucose homeostasis are treated with anti-hyperglycemics exacerbating cell starvation, inducing hypoglycemia and raising respiratory quotient. Reductions in hyperglycemia are achieved at the expense of glucose dependency and metabolic inflexibility (Gibas & Gibas, 2017). The brain is not immune from these cycles of starvation. The bioenergetic model characterizes propagation of late-onset, sporadic Alzheimer's disease as loss of molecular fidelity and compromised energy originating in brain networks with highest metabolic demand...
September 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28892789/thymoquinone-rich-fraction-nanoemulsion-tqrfne-decreases-a%C3%AE-40-and-a%C3%AE-42-levels-by-modulating-app-processing-up-regulating-ide-and-lrp1-and-down-regulating-bace1-and-rage-in-response-to-high-fat-cholesterol-diet-induced-rats
#7
Norsharina Ismail, Maznah Ismail, Nur Hanisah Azmi, Muhammad Firdaus Abu Bakar, Zhang Yida, Maizaton Atmadini Abdullah, Hamidon Basri
Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis...
September 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28877460/persistence-of-pancreatic-insulin-mrna-expression-and-proinsulin-protein-in-type-1-diabetes-pancreata
#8
Clive Wasserfall, Harry S Nick, Martha Campbell-Thompson, Dawn Beachy, Leena Haataja, Irina Kusmartseva, Amanda Posgai, Maria Beery, Christopher Rhodes, Ezio Bonifacio, Peter Arvan, Mark Atkinson
The canonical notion that type 1 diabetes (T1D) results following a complete destruction of β cells has recently been questioned as small amounts of C-peptide are detectable in patients with long-standing disease. We analyzed protein and gene expression levels for proinsulin, insulin, C-peptide, and islet amyloid polypeptide within pancreatic tissues from T1D, autoantibody positive (Ab+), and control organs. Insulin and C-peptide levels were low to undetectable in extracts from the T1D cohort; however, proinsulin and INS mRNA were detected in the majority of T1D pancreata...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28870559/intranasal-deferoxamine-affects-memory-loss-oxidation-and-the-insulin-pathway-in-the-streptozotocin-rat-model-of-alzheimer-s-disease
#9
J M Fine, A C Forsberg, B M Stroebel, K A Faltesek, D R Verden, K A Hamel, E B Raney, J M Crow, L R Haase, K E Knutzen, K D Kaczmarczek, W H Frey, L R Hanson
Accumulation of metal and the accompanying increase in oxidative stress and inflammation plays an important role in neurodegenerative disease. Deferoxamine (DFO) is a metal chelator found to be beneficial in several animal models of neurodegenerative disease and insult including Alzheimer's disease, Parkinson's disease, stroke, and subarachnoid hemorrhage. In this study, we determine whether intranasally (IN) administered DFO is beneficial in the intracerebroventricular streptozotocin (ICV STZ) rat model of sporadic Alzheimer's disease, which is different from previous models in that it exhibits dysregulation of insulin metabolism as well as oxidative stress and inflammation...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28856782/activity-of-zn-and-mg-phthalocyanines-and-porphyrazines-in-amyloid-aggregation-of-insulin
#10
V Kovalska, S Chernii, M Losytskyy, J Ostapko, I Tretyakova, A Gorski, V Chernii, S Yarmoluk
Formation of the deposits of protein aggregates-amyloid fibrils in an intracellular and intercellular space-is common to a large group of amyloid-associated disorders. Among the approaches to develop of therapy of such disorders is the use of agents preventing protein fibrillization. Polyaromatic complexes-porphyrins and phthalocyanines-are known as compounds possessing anti-fibrillogenic activity. Here, we explore the impact of related macrocyclic complexes-phthalocyanines (Pc) and octaphenyl porphyrazines (Pz) of Mg and Zn-on aggregation of amyloidogenic protein insulin...
August 30, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28852028/insulin-resistance-is-associated-with-reductions-in-specific-cognitive-domains-and-increases-in-csf-tau-in-cognitively-normal-adults
#11
Simon M Laws, Scott Gaskin, Amy Woodfield, Velandai Srikanth, David Bruce, Paul E Fraser, Tenielle Porter, Philip Newsholme, Nadeeja Wijesekara, Samantha Burnham, Vincent Doré, Qiao-Xin Li, Paul Maruff, Colin L Masters, Stephanie Rainey-Smith, Christopher C Rowe, Olivier Salvado, Victor L Villemagne, Ralph N Martins, Giuseppe Verdile
Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer's disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear. Here we investigate the relationship of indices of IR (HOMA-IR) and pancreatic β-cell function (HOMA-B) with cognitive performance across several domains (Verbal/Visual Episodic Memory, Executive Function, Language and a measure of Global cognition) and AD biomarkers (CSF Aβ42, T-tau/P-tau, hippocampal volume and neocortical Aβ-amyloid burden)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844000/epigallocatechin-gallate-induces-extracellular-degradation-of-amyloid-%C3%AE-protein-by-increasing-neprilysin-secretion-from-astrocytes-through-activation-of-erk-and-pi3k-pathways
#12
Naoki Yamamoto, Mari Shibata, Ryo Ishikuro, Mamoru Tanida, Yuina Taniguchi, Yuri Ikeda-Matsuo, Kazuya Sobue
Amyloid-β (Aβ) production and clearance in the brain is a crucial focus of investigations into the pathogenesis of Alzheimer disease. Imbalance between production and clearance leads to accumulation of Aβ. The important Aβ-degrading enzymes in the brain are neprilysin (NEP) and insulin-degrading enzyme (IDE), and defective enzyme expression may facilitate Aβ deposition in sporadic late-onset AD patients. It has been suggested that epigallocatechin gallate (EGCG), a member of the catechin family, might be an effective treatment for AD, because it has been shown to elevate NEP expression...
August 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28840430/mevastatin-promotes-neuronal-survival-against-a%C3%AE-induced-neurotoxicity-through-ampk-activation
#13
Edy Kornelius, Hsin-Hua Li, Chiung-Huei Peng, Hui-Wen Hsiao, Yi-Sun Yang, Chien-Ning Huang, Chih-Li Lin
Statins or HMG-CoA reductase inhibitors have been shown to be effective at lowering cholesterol levels, and the application of these molecules has gradually emerged as an attractive therapeutic strategy for neurodegenerative diseases. Epidemiological studies suggest that statin use is associated with a decreased incidence of Alzheimer's disease (AD). Thus, statins may play a beneficial role in reducing amyloid β (Aβ) toxicity, the most relevant pathological feature and pathogenesis of AD. However, the precise mechanisms involved in statin-inhibited Aβ toxicity remain unclear...
August 24, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28832656/involvement-of-insulin-resistance-in-d-galactose-induced-age-related-dementia-in-rats-protective-role-of-metformin-and-saxagliptin
#14
Sara Kenawy, Rehab Hegazy, Azza Hassan, Siham El-Shenawy, Nawal Gomaa, Hala Zaki, Amina Attia
Age-related dementia is one of the most devastating disorders affecting the elderly. Recently, emerging data suggest that impaired insulin signaling is the major contributor in the development of Alzheimer's dementia (AD), which is the most common type of senile dementia. In the present study, we investigated the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents, in a rat model of brain aging and AD using D-galactose (D-gal, 150 mg/kg/day, s.c. for 90 successive days)...
2017: PloS One
https://www.readbyqxmd.com/read/28832427/resistance-training-reduces-inflammation-and-fatigue-and-improves-physical-function-in-older-breast-cancer-survivors
#15
Monica C Serra, Alice S Ryan, Heidi K Ortmeyer, Odessa Addison, Andrew P Goldberg
OBJECTIVE: Resistance training (RT) reduces fatigue and improves physical function and quality of life (QOL) in breast cancer survivors (BCS). This may be related to reductions in systemic and tissue-specific inflammation. This pilot study examines the hypothesis that RT induces changes in systemic and tissue-specific inflammation that contribute to improvements in physical and behavioral function in postmenopausal BCS. METHODS: Eleven BCS (60 ± 2 years old, body mass index 30 ± 1 kg/m, mean ± SEM) underwent assessments of fatigue (Piper Fatigue Scale), physical function, QOL (SF-36), glucose and lipid metabolism, and systemic, skeletal muscle, and adipose tissue inflammation (n = 9) before and after 16 weeks of moderate-intensity whole-body RT...
August 21, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28829122/olive-component-oleuropein-promotes-%C3%AE-cell-insulin-secretion-and-protects-%C3%AE-cells-from-amylin-amyloid-induced-cytotoxicity
#16
Ling Wu, Paul Velander, Dongmin Liu, Bin Xu
Oleuropein, a natural product derived from olive leaves, has reported anti-diabetic functions. However, detailed molecular mechanisms for how it affects β-cell functions remain poorly understood. Here, we present evidence that oleuropein promotes glucose-stimulated insulin secretion (GSIS) in β-cells. The effect is dose-dependent and stimulates the ERK/MAPK signaling pathway. We further demonstrated that oleuropein inhibits the cytotoxicity induced by amylin amyloids, a hallmark feature of type 2 diabetes...
September 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28821639/amyloid-induced-%C3%AE-cell-dysfunction-and-islet-inflammation-are-ameliorated-by-4-phenylbutyrate-pba-treatment
#17
Joel Montane, Sara de Pablo, Carlos Castaño, Júlia Rodríguez-Comas, Lisa Cadavez, Mercè Obach, Montse Visa, Gema Alcarraz-Vizán, Melchor Sanchez-Martinez, Alfons Nonell-Canals, Marcelina Parrizas, Joan-Marc Servitja, Anna Novials
Human islet amyloid polypeptide (hIAPP) aggregation is associated with β-cell dysfunction and death in type 2 diabetes (T2D). we aimed to determine whether in vivo treatment with chemical chaperone 4-phenylbutyrate (PBA) ameliorates hIAPP-induced β-cell dysfunction and islet amyloid formation. Oral administration of PBA in transgenic (Tg) mice expressing hIAPP in pancreatic β cells (hIAPP Tg) counteracted impaired glucose homeostasis and restored glucose-stimulated insulin secretion. Moreover, PBA treatment almost completely prevented the transcriptomic alterations observed in hIAPP Tg islets, including the induction of genes related to inflammation...
August 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28818314/comparison-of-disaggregative-effect-of-a-type-egcg-dimer-and-egcg-monomer-on-the-preformed-bovine-insulin-amyloid-fibrils
#18
Rong-Zu Nie, Wei Zhu, Jin-Ming Peng, Zhen-Zhen Ge, Chun-Mei Li
In the present study, the disruptive effects of epigallocatechin-3-gallate (EGCG) and A-type dimeric epigallocatechin-3-gallate (A-type EGCG dimer) on the preformed bovine insulin amyloid fibrils were studied by several biophysical methods including thioflavin-T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic (ANS) fluorescence assay, Congo red (CR) binding assay, dynamic light scattering (DLS), transmission electron microscopy (TEM), Gel electrophoresis (SDS-PAGE) and Bradford assay. Our results demonstrated that A-type EGCG dimer showed significantly more potential disaggregative effects on the bovine insulin amyloid fibrils than EGCG...
July 31, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28814391/filling-the-void-a-role-for-exercise-induced-bdnf-and-brain-amyloid-precursor-protein-processing
#19
Rebecca Ek MacPherson
Inactivity, obesity, and insulin resistance are significant risk factors for the development of Alzheimer's disease (AD). Several studies have demonstrated that diet induced obesity, inactivity, and insulin resistance exacerbates neuropathological hallmarks of AD. The aggregation of beta-amyloid peptides is one of these hallmarks. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid precursor protein (APP) processing, leading to beta-amyloid peptide formation...
August 16, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28812049/importance-of-adiponectin-activity-in-the-pathogenesis-of-alzheimer-s-disease
#20
REVIEW
Masaaki Waragai, Gilbert Ho, Yoshiki Takamatsu, Kazunari Sekiyama, Shuei Sugama, Takato Takenouchi, Eliezer Masliah, Makoto Hashimoto
A recent study suggested that insulin resistance may play a central role in the pathogenesis of Alzheimer's disease (AD). In this regard, it is of note that upregulation of plasma adiponectin (APN), a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation, has recently been associated with the severities of amyloid deposits and cognitive deficits in the elderly, suggesting that APN may enhance the risk of AD. These results are unanticipated because AD has been linked to type II diabetes and other metabolic disorders in which hypoadiponectinemia has been firmly established, and because APN ameliorated neuropathological features in a mouse model of neurodegeneration...
August 2017: Annals of Clinical and Translational Neurology
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