scholarly journals Role of mitochondrial phosphate carrier in metabolism–secretion coupling in rat insulinoma cell line INS-1

2011 ◽  
Vol 435 (2) ◽  
pp. 421-430 ◽  
Author(s):  
Yuichi Nishi ◽  
Shimpei Fujimoto ◽  
Mayumi Sasaki ◽  
Eri Mukai ◽  
Hiroki Sato ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Critical Role ◽  
Mitochondrial Fraction ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Atp Production ◽  
Insulinoma Cell ◽  
Consequent Reduction ◽  
Phosphate Carrier

In pancreatic β-cells, glucose-induced mitochondrial ATP production plays an important role in insulin secretion. The mitochondrial phosphate carrier PiC is a member of the SLC25 (solute carrier family 25) family and transports Pi from the cytosol into the mitochondrial matrix. Since intramitochondrial Pi is an essential substrate for mitochondrial ATP production by complex V (ATP synthase) and affects the activity of the respiratory chain, Pi transport via PiC may be a rate-limiting step for ATP production. We evaluated the role of PiC in metabolism–secretion coupling in pancreatic β-cells using INS-1 cells manipulated to reduce PiC expression by siRNA (small interfering RNA). Consequent reduction of the PiC protein level decreased glucose (10 mM)-stimulated insulin secretion, the ATP:ADP ratio in the presence of 10 mM glucose and elevation of intracellular calcium concentration in response to 10 mM glucose without affecting the mitochondrial membrane potential (Δψm) in INS-1 cells. In experiments using the mitochondrial fraction of INS-1 cells in the presence of 1 mM succinate, PiC down-regulation decreased ATP production at various Pi concentrations ranging from 0.001 to 10 mM, but did not affect Δψm at 3 mM Pi. In conclusion, the Pi supply to mitochondria via PiC plays a critical role in ATP production and metabolism–secretion coupling in INS-1 cells.

CFTR silencing in pancreatic β-cells reveals a functional impact on glucose-stimulated insulin secretion and oxidative stress response

2016 ◽  
Vol 310 (3) ◽  
pp. E200-E212 ◽  
Author(s):  
Thierry Ntimbane ◽  
Geneviève Mailhot ◽  
Schohraya Spahis ◽  
Remi Rabasa-Lhoret ◽  
Marie-Laure Kleme ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Insulin Secretion ◽  
Inflammatory Responses ◽  
Lipid Peroxides ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Min6 Cells ◽  
Atp Production

Cystic fibrosis (CF)-related diabetes (CFRD) has become a critical complication that seriously affects the clinical outcomes of CF patients. Although CFRD has emerged as the most common nonpulmonary complication of CF, little is known about its etiopathogenesis. Additionally, whether oxidative stress (OxS), a common feature of CF and diabetes, influences CFRD pathophysiology requires clarification. The main objective of this study was to shed light on the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in combination with OxS in insulin secretion from pancreatic β-cells. CFTR silencing was accomplished in MIN6 cells by stable expression of small hairpin RNAs (shRNA), and glucose-induced insulin secretion was evaluated in the presence and absence of the valuable prooxidant system iron/ascorbate (Fe/Asc; 0.075/0.75 mM) along with or without the antioxidant Trolox (1 mM). Insulin output from CFTR-silenced MIN6 cells was significantly reduced (∼70%) at basal and at different glucose concentrations compared with control Mock cells. Furthermore, CFTR silencing rendered MIN6 cells more sensitive to OxS as evidenced by both increased lipid peroxides and weakened antioxidant defense, especially following incubation with Fe/Asc. The decreased insulin secretion in CFTR-silenced MIN6 cells was associated with high levels of NF-κB (the major participant in inflammatory responses), raised apoptosis, and diminished ATP production in response to the Fe/Asc challenge. However, these defects were alleviated by the addition of Trolox, thereby pointing out the role of OxS in aggravating the effects of CFTR deficiency. Our findings indicate that CFTR deficiency in combination with OxS may contribute to endocrine cell dysfunction and insulin secretion, which at least in part may explain the development of CFRD.

scholarly journals Bimodal role of conventional protein kinase C in insulin secretion from rat pancreatic β cells

2004 ◽  
Vol 561 (1) ◽  
pp. 133-147 ◽  
Author(s):  
Hui Zhang ◽  
Masahiro Nagasawa ◽  
Satoko Yamada ◽  
Hideo Mogami ◽  
Yuko Suzuki ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Kinase C

scholarly journals Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells

2019 ◽  
Vol 27 ◽  
pp. S81-S91 ◽  
Author(s):  
Mica Ohara-Imaizumi ◽  
Kyota Aoyagi ◽  
Toshihisa Ohtsuka
Keyword(s):  
Insulin Secretion ◽  
Active Zone ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Involvement of a Mitochondrial Phosphatase in the Regulation of ATP Production and Insulin Secretion in Pancreatic β Cells

2005 ◽  
Vol 19 (2) ◽  
pp. 197-207 ◽  
Author(s):  
David J. Pagliarini ◽  
Sandra E. Wiley ◽  
Michelle E. Kimple ◽  
Jesse R. Dixon ◽  
Patrick Kelly ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Atp Production
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