scholarly journals Preparation of Polymeric Films of PVDMA–PEI Functionalized with Fatty Acids for Studying the Adherence and Proliferation of Langerhans β-Cells

ACS Omega ◽  
2020 ◽  
Vol 5 (10) ◽  
pp. 5249-5257 ◽  
Author(s):  
Martha E. Ávila-Cossío ◽  
Ignacio A. Rivero ◽  
Victor García-González ◽  
Manuel Alatorre-Meda ◽  
Eustolia Rodríguez-Velázquez ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polymeric Films ◽  
Β Cells

scholarly journals Insulin secretion in health and disease: nutrients dictate the pace

2015 ◽  
Vol 75 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Romano Regazzi ◽  
Adriana Rodriguez-Trejo ◽  
Cécile Jacovetti
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Cell Mass ◽  
Insulin Biosynthesis ◽  
Β Cells ◽  
Β Cell ◽  
Altered Expression ◽  
Cell Dysfunction ◽  
Dietary Nutrients ◽  
Underlying Mechanisms

Insulin is a key hormone controlling metabolic homeostasis. Loss or dysfunction of pancreatic β-cells lead to the release of insufficient insulin to cover the organism needs, promoting diabetes development. Since dietary nutrients influence the activity of β-cells, their inadequate intake, absorption and/or utilisation can be detrimental. This review will highlight the physiological and pathological effects of nutrients on insulin secretion and discuss the underlying mechanisms. Glucose uptake and metabolism in β-cells trigger insulin secretion. This effect of glucose is potentiated by amino acids and fatty acids, as well as by entero-endocrine hormones and neuropeptides released by the digestive tract in response to nutrients. Glucose controls also basal and compensatory β-cell proliferation and, along with fatty acids, regulates insulin biosynthesis. If in the short-term nutrients promote β-cell activities, chronic exposure to nutrients can be detrimental to β-cells and causes reduced insulin transcription, increased basal secretion and impaired insulin release in response to stimulatory glucose concentrations, with a consequent increase in diabetes risk. Likewise, suboptimal early-life nutrition (e.g. parental high-fat or low-protein diet) causes altered β-cell mass and function in adulthood. The mechanisms mediating nutrient-induced β-cell dysfunction include transcriptional, post-transcriptional and translational modifications of genes involved in insulin biosynthesis and secretion, carbohydrate and lipid metabolism, cell differentiation, proliferation and survival. Altered expression of these genes is partly caused by changes in non-coding RNA transcripts induced by unbalanced nutrient uptake. A better understanding of the mechanisms leading to β-cell dysfunction will be critical to improve treatment and find a cure for diabetes.

Effects of pharmacological inhibition of NADPH oxidase or iNOS on pro-inflammatory cytokine, palmitic acid or H2O2-induced mouse islet or clonal pancreatic β-cell dysfunction

2010 ◽  
Vol 30 (6) ◽  
pp. 445-453 ◽  
Author(s):  
Marta Michalska ◽  
Gabriele Wolf ◽  
Reinhard Walther ◽  
Philip Newsholme
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Nadph Oxidase ◽  
Inflammatory Cytokine ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Mouse Islets ◽  
Pro Inflammatory Cytokines

Various pancreatic β-cell stressors including cytokines and saturated fatty acids are known to induce oxidative stress, which results in metabolic disturbances and a reduction in insulin secretion. However, the key mechanisms underlying dysfunction are unknown. We investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines, H2O2 or PA (palmitic acid) on β-cell insulin secretion, ATP, the NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) component p47phox and iNOS (inducible nitric oxide synthase) levels using primary mouse islets or clonal rat BRIN-BD11 β-cells. Addition of a pro-inflammatory cytokine mixture [IL-1β (interleukin-1β), TNF-α (tumour necrosis factor-α) and IFN-γ (interferon-γ)] or H2O2 (at sub-lethal concentrations) inhibited chronic (24 h) levels of insulin release by at least 50% (from islets and BRIN-BD11 cells), while addition of the saturated fatty acid palmitate inhibited acute (20 min) stimulated levels of insulin release from mouse islets. H2O2 decreased ATP levels in the cell line, but elevated p47phox and iNOS levels as did cytokine addition. Similar effects were observed in mouse islets with respect to elevation of p47phox and iNOS levels. Addition of antioxidants SOD (superoxide dismutase), Cat (catalase) and NAC (N-acetylcysteine) attenuated H2O2 or the saturated fatty acid palmitate-dependent effects, but not cytokine-induced dysfunction. However, specific chemical inhibitors of NADPH oxidase and/or iNOS appear to significantly attenuate the effects of cytokines, H2O2 or fatty acids in islets. While pro-inflammatory cytokines are known to increase p47phox and iNOS levels in β-cells, we now report that H2O2 can increase levels of the latter two proteins, suggesting a key role for positive-feedback redox sensitive regulation of β-cell dysfunction.

Free fatty acids stimulate autophagy in pancreatic β-cells via JNK pathway

2010 ◽  
Vol 401 (4) ◽  
pp. 561-567 ◽  
Author(s):  
Koji Komiya ◽  
Toyoyoshi Uchida ◽  
Takashi Ueno ◽  
Masato Koike ◽  
Hiroko Abe ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Jnk Pathway

Vitamin D and Omega-3 Polyunsaturated Fatty Acids in Type 1 Diabetes modulation

2022 ◽  
Vol 22 ◽  
Author(s):  
Thais Sibioni Berti Bastos ◽  
Tárcio Teodoro Braga ◽  
Mariana Rodrigues Davanso
Keyword(s):  
Fatty Acids ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Polyunsaturated Fatty Acids ◽  
Immune Cell ◽  
Omega 3 ◽  
Β Cells ◽  
Potential Benefits ◽  
Chronic Autoimmune Disease

Background: Type 1 diabetes (T1D) is a chronic autoimmune disease that affects people globally. Usually developed during childhood, T1D is characterized by the destruction of pancreatic β-cells due to immune cell attack and the establishment of an inflammatory process. Objective: The study aimed to investigate the effects of vitamin D through its nuclear receptor and the ω-3 polyunsaturated fatty acids (PUFAs) through their lipid derivatives in T1D modulation. Both components exert anti-inflammatory activity and act directly on cells of the immune system, attenuating the destruction of insulin-producing cells. Furthermore, they lead to a better glycemic level, reducing the need for insulin and a normal immune state, such as C-peptide maintenance. Method: Presently, our review highlights the significant studies that evaluated the supplementation of vitamin D and ω-3 PUFAs in humans and animal models in the modulation of T1D. Conclusion: The data collected suggests that supplementation can provide potential benefits, mainly when done early in the diagnosis, since it reduces the need for insulin and the risk of complications generated by the disease.

Effects of palmitate on ER and cytosolic Ca2+ homeostasis in β-cells

2009 ◽  
Vol 296 (4) ◽  
pp. E690-E701 ◽  
Author(s):  
Kamila S. Gwiazda ◽  
Ting-Lin B. Yang ◽  
Yalin Lin ◽  
James D. Johnson
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Cell Function ◽  
Fluorescent Protein ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

There are strong links between obesity, elevated free fatty acids, and type 2 diabetes. Specifically, the saturated fatty acid palmitate has pleiotropic effects on β-cell function and survival. In the present study, we sought to determine the mechanism by which palmitate affects intracellular Ca2+, and in particular the role of the endoplasmic reticulum (ER). In human β-cells and MIN6 cells, palmitate rapidly increased cytosolic Ca2+ through a combination of Ca2+ store release and extracellular Ca2+ influx. Palmitate caused a reversible lowering of ER Ca2+, measured directly with the fluorescent protein-based ER Ca2+ sensor D1ER. Using another genetically encoded indicator, we observed long-lasting oscillations of cytosolic Ca2+ in palmitate-treated cells. In keeping with this observed ER Ca2+ depletion, palmitate induced rapid phosphorylation of the ER Ca2+ sensor protein kinase R-like ER kinase (PERK) and subsequently ER stress and β-cell death. We detected little palmitate-induced insulin secretion, suggesting that these Ca2+ signals are poorly coupled to exocytosis. In summary, we have characterized Ca2+-dependent mechanisms involved in altered β-cell function and survival induced by the free fatty acid palmitate. We present the first direct evidence that free fatty acids reduce ER Ca2+ and shed light on pathways involved in lipotoxicity and the pathogenesis of type 2 diabetes.

Life and death decisions of the pancreatic β-cell: the role of fatty acids

2006 ◽  
Vol 112 (1) ◽  
pp. 27-42 ◽  
Author(s):  
Philip Newsholme ◽  
Deirdre Keane ◽  
Hannah J. Welters ◽  
Noel G. Morgan
Keyword(s):  
Fatty Acids ◽  
Insulin Release ◽  
Chronic Exposure ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Endogenous Fatty Acid ◽  
Gene And Protein Expression ◽  
Β Cell Function

Both stimulatory and detrimental effects of NEFAs (non-esterified fatty acids) on pancreatic β-cells have been recognized. Acute exposure of the pancreatic β-cell to high glucose concentrations and/or saturated NEFAs results in a substantial increase in insulin release, whereas chronic exposure results in desensitization and suppression of secretion, followed by induction of apoptosis. Some unsaturated NEFAs also promote insulin release acutely, but they are less toxic to β-cells during chronic exposure and can even exert positive protective effects. Therefore changes in the levels of NEFAs are likely to be important for the regulation of β-cell function and viability under physiological conditions. In addition, the switching between endogenous fatty acid synthesis or oxidation in the β-cell, together with alterations in neutral lipid accumulation, may have critical implications for β-cell function and integrity. Long-chain acyl-CoA (formed from either endogenously synthesized or exogenous fatty acids) controls several aspects of β-cell function, including activation of specific isoenzymes of PKC (protein kinase C), modulation of ion channels, protein acylation, ceramide formation and/or NO-mediated apoptosis, and transcription factor activity. In this review, we describe the effects of exogenous and endogenous fatty acids on β-cell metabolism and gene and protein expression, and have explored the outcomes with respect to insulin secretion and β-cell integrity.

scholarly journals Inhibition of Autophagic Turnover in β-Cells by Fatty Acids and Glucose Leads to Apoptotic Cell Death

2014 ◽  
Vol 290 (10) ◽  
pp. 6071-6085 ◽  
Author(s):  
Shakeel U. R. Mir ◽  
Nicholas M. George ◽  
Lubna Zahoor ◽  
Robert Harms ◽  
Zachary Guinn ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Β Cells

scholarly journals Free Fatty Acids Induce a Proinflammatory Response in Islets via the Abundantly Expressed Interleukin-1 Receptor I

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5218-5229 ◽  
Author(s):  
Marianne Böni-Schnetzler ◽  
Simone Boller ◽  
Sarah Debray ◽  
Karim Bouzakri ◽  
Daniel T. Meier ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Interleukin 1 ◽  
Human Islets ◽  
Type I ◽  
Β Cells ◽  
Mouse Tissues ◽  
Mouse Islets ◽  
Human And Mouse ◽  
Proinflammatory Factors

Abstract Islets of patients with type 2 diabetes mellitus (T2DM) display features of an inflammatory process including elevated levels of the cytokine IL-1β, various chemokines, and macrophages. IL-1β is a master regulator of inflammation, and IL-1 receptor type I (IL-1RI) blockage improves glycemia and insulin secretion in humans with T2DM and in high-fat-fed mice pointing to a pivotal role of IL-1RI activity in intra-islet inflammation. Given the association of dyslipidemia and T2DM, we tested whether free fatty acids (FFA) promote the expression of proinflammatory factors in human and mouse islets and investigated a role for the IL-1RI in this response. A comparison of 22 mouse tissues revealed the highest IL-1RI expression levels in islets and MIN6 β-cells. FFA induced IL-1β, IL-6, and IL-8 in human islets and IL-1β and KC in mouse islets. Elevated glucose concentrations enhanced FFA-induced proinflammatory factors in human islets. Blocking the IL-1RI with the IL-1R antagonist (IL-1Ra) strongly inhibited FFA-mediated expression of proinflammatory factors in human and mouse islets. Antibody inhibition of IL-1β revealed that FFA stimulated IL-1RI activity via the induction of the receptor ligand. FFA-induced IL-1β and KC expression in mouse islets was completely dependent on the IL-1R/Toll-like receptor (TLR) docking protein Myd88 and partly dependent on TLR2 and -4. Activation of TLR2 in purified human β-cells and islets stimulated the expression of proinflammatory factors, and IL-1RI activity increased the TLR2 response in human islets. We conclude that FFA and TLR stimulation induce proinflammatory factors in islets and that IL-1RI engagement results in signal amplification.

Sign in / Sign up

Export Citation Format

Share Document