scholarly journals Mitochondrial Functional State in Clonal Pancreatic β-Cells Exposed to Free Fatty Acids

2003 ◽  
Vol 278 (22) ◽  
pp. 19709-19715 ◽  
Author(s):  
Vasilij Koshkin ◽  
Xiaolin Wang ◽  
Philipp E. Scherer ◽  
Catherine B. Chan ◽  
Michael B. Wheeler
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Functional State ◽  
Β Cells ◽  
Pancreatic Β Cells

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

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

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.

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.

scholarly journals Optical control of GPR40 signalling in pancreatic β-cells

2017 ◽  
Vol 8 (11) ◽  
pp. 7604-7610 ◽  
Author(s):  
James Allen Frank ◽  
Dmytro A. Yushchenko ◽  
Nicholas H. F. Fine ◽  
Margherita Duca ◽  
Mevlut Citir ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Function ◽  
Optical Control ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Β Cell Function

Fatty acids activate GPR40 and K+ channels to modulate β-cell function.

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