Mutated ATP synthase induces oxidative stress and impaired insulin secretion in β‐cells of female BHE/cdb rats

Saleh, Monique C.; Fatehi‐Hassanabad, Zahra; Wang, Rennian; Nino‐Fong, Rodolfo; Wadowska, Dorota; Wright, Glenda M.; Harper, Mary‐Ellen; Chan, Catherine B.

doi:10.1002/dmrr.819

Cited by 16 publications

(15 citation statements)

References 59 publications

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“…Dipeptidyl peptidase IV inhibitor (Millipore, Billerica, Mass., USA) was added to aliquots obtained at baseline and 30 min to assay gastric inhibitory polypeptide (GIP). Insulin tolerance test was conducted as published (Saleh et al 2008). Area under the curve and incremental area under the curve (IAUC) were calculated in accordance with established methods (Wolever 2004).…”

Section: Glucose and Insulin Tolerance Testsmentioning

confidence: 99%

Cooking enhances beneficial effects of pea seed coat consumption on glucose tolerance, incretin, and pancreatic hormones in high-fat-diet–fed rats

Hashemi

Yang

et al. 2015

Appl. Physiol. Nutr. Metab.

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Pulses, including dried peas, are nutrient- and fibre-rich foods that improve glucose control in diabetic subjects compared with other fibre sources. We hypothesized feeding cooked pea seed coats to insulin-resistant rats would improve glucose tolerance by modifying gut responses to glucose and reducing stress on pancreatic islets. Glucose intolerance induced in male Sprague-Dawley rats with high-fat diet (HFD; 10% cellulose as fibre) was followed by 3 weeks of HFD with fibre (10%) provided by cellulose, raw-pea seed coat (RP), or cooked-pea seed coat (CP). A fourth group consumed low-fat diet with 10% cellulose. Oral and intraperitoneal glucose tolerance tests (oGTT, ipGTT) were done. CP rats had 30% and 50% lower glucose and insulin responses in oGTT, respectively, compared with the HFD group (P < 0.05) but ipGTT was not different. Plasma islet and incretin hormone concentrations were measured. α- and β-cell areas in the pancreas and density of K- and L-cells in jejunum and ileum were quantified. Jejunal expression of hexose transporters was measured. CP feeding increased fasting glucagon-like peptide 1 and glucose-stimulated gastric inhibitory polypeptide responses (P < 0.05), but K- and L-cells densities were comparable to HFD, as was abundance of SGLT1 and GLUT2 mRNA. No significant difference in β-cell area between diet groups was observed. α-cell area was significantly smaller in CP compared with RP rats (P < 0.05). Overall, our results demonstrate that CP feeding can reverse adverse effects of HFD on glucose homeostasis and is associated with enhanced incretin secretion and reduced α-cell abundance.

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Section: Glucose and Insulin Tolerance Testsmentioning

confidence: 99%

Cooking enhances beneficial effects of pea seed coat consumption on glucose tolerance, incretin, and pancreatic hormones in high-fat-diet–fed rats

Hashemi

Yang

et al. 2015

Appl. Physiol. Nutr. Metab.

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“…invadolysin larvae are defective in a behavioral response to hypoxia ROS are not only damaging molecules, but also have an important role in cell signaling Saleh et al, 2008). Mitochondria have and blw KG5893 third-instar fat body normalized to control tissue (wt).…”

Section: Acc Is Inhibited In the Invadolysin Mutantmentioning

confidence: 99%

“…It has also been reported that increased formation of oxygen radicals increases oxidative stress in the ATP synthase subunit a (ATP5a1) mutant rat. (Saleh et al, 2008).…”

Section: Loss Of Invadolysin Affects Mitochondrial Membrane Potentialmentioning

confidence: 99%

“…These changes affect cellular energy levels and cause oxidative stress, which have dramatic and deleterious impacts on development. Mutations that affect the function of respiratory chain enzymes have been reported to affect energy levels and oxidative stress in flies, rats and humans (Bell et al, 2007;Celotto et al, 2006;Mourikis et al, 2006;Saleh et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Invadolysin, a conserved lipid droplet-associated metalloprotease, is required for mitochondrial function in Drosophila

Cara

Duca

Dunbar

et al. 2013

Journal of Cell Science

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SummaryMitochondria are the main producers of ATP, the principal energy source of the cell, and reactive oxygen species (ROS), important signaling molecules. Mitochondrial morphogenesis and function depend on a hierarchical network of mechanisms in which proteases appear to be center stage. The invadolysin gene encodes an essential conserved metalloproteinase of the M8 family that is necessary for mitosis and cell migration during Drosophila development. We previously demonstrated that invadolysin is found associated with lipid droplets in cells. Here, we present data demonstrating that invadolysin interacts physically with three mitochondrial ATP synthase subunits. Our studies have focused on the genetic phenotypes of invadolysin and bellwether, the Drosophila homolog of ATP synthase a, mutants. The invadolysin mutation presents defects in mitochondrial physiology similar to those observed in bellwether mutants. The invadolysin and bellwether mutants have parallel phenotypes that affect lipid storage and mitochondrial electron transport chain activity, which result in a reduction in ATP production and an accumulation of ROS. As a consequence, invadolysin mutant larvae show lower energetic status and higher oxidative stress. Our data demonstrate an essential role for invadolysin in mitochondrial function that is crucial for normal development and survival.

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“…In addition, some nuclear proteins, such as p300 and hepatocyte nuclear factor 4, are downstream targets of AMPK [4] . Saleh et al have reported [5] that pancreatic duodenal homeobox-1 (PDX-1) is one of the nuclear transcription factors that probably associates with AMPK to some extent. However, PDX-1 regulation by AMPK has not been confirmed in β cells.…”

Section: Introductionmentioning

confidence: 99%

AMPK enhances the expression of pancreatic duodenal homeobox-1 via PPARα, but not PPARγ, in rat insulinoma cell line INS-1

Guo

Zhang

et al. 2010

Acta Pharmacol Sin

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Aim: To investigate whether AMP-activated protein kinase (AMPK) regulates the expression of pancreatic duodenal homeobox-1 (PDX-1), a β-cell-specific transcription factor and whether PPARα/γ is involved in the regulation of pancreatic β-cell lines after acute stimulation. Methods: Rat insulinoma cell line INS-1 was treated with an activator (AICAR) or inhibitor (Compound C) of AMPK as well as inhibitors of PPARs (MK886 to PPARα and BADGE to PPARγ). The mRNA levels of PDX-1, PPARα and PPARγ were measured using real-time RT-PCR, and Western blotting was used to detect the protein expression of these factors. Results: Activation of AMPK by AICAR induced significantly increased the expression of PDX-1, and this increase was abrogated when AMPK was inactivated by Compound C. Similarly, the expression of PPARα and PPARγ was also increased by AICAR or decreased by Compound C. However AMPK activation did not increase nuclear PDX-1 protein levels when PPARα was inhibited. In contrast, AMPK activation still up-regulated PDX-1 protein levels during PPARγ inhibition. Additionally, PPARα activation induced by fenofibrate significantly enhanced nuclear PDX-1 protein expression. Conclusion: AMPK regulates the expression of PDX-1 at both the transcriptional and protein levels, and PPARα may be acutely involved in the regulation of INS-1 cells.

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Mutated ATP synthase induces oxidative stress and impaired insulin secretion in β‐cells of female BHE/cdb rats

Abstract: The findings are consistent with impaired but partially compensated mechanisms of insulin secretion early in life, but progressive non-compensated impairments due to oxidative stress occurs by age 43 weeks.

Cited by 16 publications

References 59 publications

Cooking enhances beneficial effects of pea seed coat consumption on glucose tolerance, incretin, and pancreatic hormones in high-fat-diet–fed rats

Cooking enhances beneficial effects of pea seed coat consumption on glucose tolerance, incretin, and pancreatic hormones in high-fat-diet–fed rats

Invadolysin, a conserved lipid droplet-associated metalloprotease, is required for mitochondrial function in Drosophila

AMPK enhances the expression of pancreatic duodenal homeobox-1 via PPARα, but not PPARγ, in rat insulinoma cell line INS-1

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