Regulation of glucose‐stimulated insulin secretion by <scp>ATP</scp>ase Inhibitory Factor 1 (<scp>IF</scp>1)

Kahancová, Anežka; Sklenář, Filip; Ježek, Petr; Dlasková, Andrea

doi:10.1002/1873-3468.12991

Cited by 34 publications

(47 citation statements)

References 53 publications

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“…C0018009). The results were invariant of the source as documented in previous reports [ 8 , 11 , 12 , 38 , 39 ]. Cells were cultivated with 11-mM glucose in RPMI 1640 medium with l -glutamine, supplemented with 10-mM HEPES, 1-mM pyruvate, 5% ( v/v ) fetal calf serum, 50-μmol/L mercaptoethanol, 50 IU/mL penicillin and 50-μg/mL streptomycin [ 38 , 39 ].…”

Section: Methodssupporting

confidence: 83%

“…We found that also the inhibitory factor IF1 of the mitochondrial ATP synthase belongs to the key proteins, ensuring the physiological range of the glucose sensor [ 11 , 12 ]. The IF1 slightly inhibits synthesis of ATP, thus setting the range for elevation of phosphorylating respiration and insulin release above 3-mM glucose [ 11 , 13 ], with half-activation between 3.5 and 4-mM and saturation above 8-mM glucose [ 11 , 12 ]. When such a slight in vivo inhibition was largely cancelled using the silencing of IF1, the elevation of respiration and OXPHOS occurred at very low glucose concentration approaching to zero [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Another peculiar aspect of the pancreatic β-cell glucose sensor is the steepness of the related dose–response, i.e., insulin release dependence vs. glucose concentration [ 11 , 12 , 14 , 15 , 16 ]. The revealed narrowing of mitochondrial cristae may hypothetically contribute to this steepness, such as observed in INS-1E cells during GSIS [ 17 ] or upon the increased load of cell-permeant Krebs cycle substrate [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Glucose-Induced Expression of DAPIT in Pancreatic β-Cells

et al. 2020

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Transcript levels for selected ATP synthase membrane FO-subunits—including DAPIT—in INS-1E cells were found to be sensitive to lowering glucose down from 11 mM, in which these cells are routinely cultured. Depending on conditions, the diminished mRNA levels recovered when glucose was restored to 11 mM; or were elevated during further 120 min incubations with 20-mM glucose. Asking whether DAPIT expression may be elevated by hyperglycemia in vivo, we studied mice with hyaluronic acid implants delivering glucose for up to 14 days. Such continuous two-week glucose stimulations in mice increased DAPIT mRNA by >5-fold in isolated pancreatic islets (ATP synthase F1α mRNA by 1.5-fold). In INS-1E cells, the glucose-induced ATP increment vanished with DAPIT silencing (6% of ATP rise), likewise a portion of the mtDNA-copy number increment. With 20 and 11-mM glucose the phosphorylating/non-phosphorylating respiration rate ratio diminished to ~70% and 96%, respectively, upon DAPIT silencing, whereas net GSIS rates accounted for 80% and 90% in USMG5/DAPIT-deficient cells. Consequently, the sufficient DAPIT expression and complete ATP synthase assembly is required for maximum ATP synthesis and mitochondrial biogenesis, but not for insulin secretion as such. Elevated DAPIT expression at high glucose further increases the ATP synthesis efficiency.

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Section: Methodssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glucose-Induced Expression of DAPIT in Pancreatic β-Cells

et al. 2020

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“…Low mitochondrial ATP synthesis efficiency thus appears to ensure that the membrane potential as well as the mitochondrial and cytosolic ATP/ADP ratios are kept relatively low when insulin secretion is not required. Interestingly in this respect, ATPase inhibitory factor 1 has recently also been shown to dampen insulin secretion from insulinoma cells at basal glucose concentrations through inhibition of ATP synthesis [40] .…”

Section: Control Of Atp Flux By Atp Supplymentioning

confidence: 99%

Control of pancreatic β-cell bioenergetics

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Alberts

Barlow

et al. 2018

Biochemical Society Transactions

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The canonical model of glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells predicts a glucose-induced rise in the cytosolic ATP/ADP ratio. Such bioenergetic sensitivity to metabolic fuel is unusual as it implies that ATP flux is governed, to a significant extent, by ATP supply, while it is predominantly demand-driven in other cell types. Metabolic control is generally shared between different processes, but potential control of ATP consumption over β-cell bioenergetics has been largely ignored to date. The present paper offers a brief overview of experimental evidence that demonstrates ATP flux control by glucose-fuelled oxidative phosphorylation. Based on old and new data, it is argued that ATP supply does not hold exclusive control over ATP flux, but shares it with ATP demand, and that the distribution of control is flexible. Quantification of the bioenergetic control distribution will be important from basic and clinical perspectives, but precise measurement of the cytosolic ATP/ADP ratio is complicated by adenine nucleotide compartmentalisation. Metabolic control analysis of β-cell bioenergetics will likely clarify the mechanisms by which glucose and fatty acids amplify and potentiate GSIS, respectively. Moreover, such analysis may offer hints as to how ATP flux control shifts from ATP supply to ATP demand during the development of type 2 diabetes, and why prolonged sulfonylurea treatment causes β-cell deterioration.

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“…The recently discovered aspect has explained the adjustment of the range of glucose concentrations for the glucose sensor [ 16 ]. Surprisingly, this is ensured by the inhibitory factor protein IF-1 of the mitochondrial ATP-synthase.…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

et al. 2018

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Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased β-cell survival. Lipotoxicity is exerted by saturated FAs, whereas ω-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by β-cells, leads to an inevitable failure of pancreatic β-cells.

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Regulation of glucose‐stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

Cited by 34 publications

References 53 publications

Glucose-Induced Expression of DAPIT in Pancreatic β-Cells

Glucose-Induced Expression of DAPIT in Pancreatic β-Cells

Control of pancreatic β-cell bioenergetics

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

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