Free fatty acids increase cytosolic free calcium and stimulate insulin secretion from β-cells through activation of GPR40

2007 ◽  
Vol 263 (1-2) ◽  
pp. 173-180 ◽  
Author(s):  
Susanne Schnell ◽  
Michael Schaefer ◽  
Christof Schöfl
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Free Fatty Acids ◽  
Free Calcium ◽  
Β Cells ◽  
Cytosolic Free Calcium ◽  
Stimulate Insulin Secretion

Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40

Nature ◽  
2003 ◽  
Vol 422 (6928) ◽  
pp. 173-176 ◽  
Author(s):  
Yasuaki Itoh ◽  
Yuji Kawamata ◽  
Masataka Harada ◽  
Makoto Kobayashi ◽  
Ryo Fujii ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Free Fatty Acids ◽  
Β Cells ◽  
Pancreatic 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.

scholarly journals Associations of Free Fatty Acids With Insulin Secretion and Action Among African-American and European-American Girls and Women

Obesity ◽  
2010 ◽  
Vol 18 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Laura Lee T. Goree ◽  
Betty E. Darnell ◽  
Robert A. Oster ◽  
Marian A. Brown ◽  
Barbara A. Gower
Keyword(s):  
Fatty Acids ◽  
African American ◽  
Insulin Secretion ◽  
Free Fatty Acids ◽  
European American

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

scholarly journals Role and mechanism of rosiglitazone on the impairment of insulin secretion induced by free fatty acids on isolated rat islets

2006 ◽  
Vol 119 (7) ◽  
pp. 574-580 ◽  
Author(s):  
Jing-yan TIAN ◽  
Guo LI ◽  
Yan-yun GU ◽  
Hong-li ZHANG ◽  
Wen-zhong ZHOU ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Free Fatty Acids ◽  
Rat Islets ◽  
Isolated Rat Islets ◽  
Isolated Rat

Effects of free fatty acids on insulin secretion in obesity

2002 ◽  
Vol 3 (2) ◽  
pp. 103-112 ◽  
Author(s):  
S. Zraika ◽  
M. Dunlop ◽  
J. Proietto ◽  
S. Andrikopoulos
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Free Fatty Acids

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.

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