Glycerol 3-phosphate-induced ATP production in intact mitochondria from pancreatic B-cells

Idahl, L; Lembert, Nicolas

doi:10.1042/bj3120287

Cited by 34 publications

(21 citation statements)

References 31 publications

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“…233,269,323,326,427,459). Maechler et al (323) reported that methyl-pyruvate (rather than pyruvate) supported matrix Ca 2ϩ accumulation and insulin secretion from ␣-toxin-permeabilized INS-1 cells (323).…”

Section: Permeabilized Cell Preparationsmentioning

confidence: 99%

“…The paucity of respiratory studies on isolated ␤-cell mitochondria or permeabilized cell preparations, perhaps exacerbated by the apparent difficulty of such preparations to utilize complex I, has meant that such studies are virtually nonexistent, and it is surprisingly difficult to locate any publications employing isolated mitochondria, or permeabilized ␤-cells, exposed to these substrates. One exception was the use of luciferase to detect ATP generation by a heterogeneous preparation of mito-chondria isolated by centrifugation from ob/ob mouse islets (233,289 Ϫ1 for pyruvate, although in the apparent absence of added CoA or carnitine it is difficult to see how the fatty acids could be activated.…”

Section: E Fatty Acidsmentioning

confidence: 99%

“…Thus the 1 million ␤-cells in a mouse account for Ͻ1% of the mass of the pancreas (52), while many of the cells within the islet are not ␤-cells. Indeed, the only functional studies on islet mitochondria of which I am aware isolated minute quantities of mitochondria from ob/ob mouse islets and used the sensitive luciferase assay to detect oxidative phosphorylation, since the low yield of material precluded conventional techniques, such as respirometry (233,289,290). The greater yield of cells from insulinomas, either obtained directly from the experimental animal (91, 418), or from established cell lines (91), have allowed a very limited number of classical isolated mitochondrial studies to be performed, as well as assays of enzyme levels in mitochondria isolated from insulinoma cells (71,312).…”

Section: B Isolated Mitochondriamentioning

confidence: 99%

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The Pancreatic β-Cell: A Bioenergetic Perspective

Nicholls

2016

Physiological Reviews

123

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The pancreatic ␤-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasma membrane ion channels. The control mechanisms responsible for the unique responsiveness of the cell to glucose availability are discussed from bioenergetic and metabolic control standpoints. The concept of coupling factor facilitation of secretion is critiqued, and an attempt is made to unravel the bioenergetic basis of the oscillatory mechanisms controlling secretion. The need to consider the physiological constraints operating in the intact cell is emphasized throughout. The aim is to provide a coherent pathway through an extensive, complex, and sometimes bewildering literature, particularly for those unfamiliar with the field.

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Section: Permeabilized Cell Preparationsmentioning

confidence: 99%

Section: E Fatty Acidsmentioning

confidence: 99%

Section: B Isolated Mitochondriamentioning

confidence: 99%

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The Pancreatic β-Cell: A Bioenergetic Perspective

Nicholls

2016

Physiological Reviews

123

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“…A mitochondrial fraction from AQP3 ϩ/ϩ mouse epidermis was obtained as described previously (7). Mitochondrial ATP production was assayed as described previously (13).…”

Section: Mice Aqp3mentioning

confidence: 99%

Prevention of Skin Tumorigenesis and Impairment of Epidermal Cell Proliferation by Targeted Aquaporin-3 Gene Disruption

Hara‐Chikuma

Verkman

2008

Molecular and Cellular Biology

223

206

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Aquaporin-3 (AQP3) is a water/glycerol-transporting protein expressed strongly at the plasma membranes of basal epidermal cells in skin. We found that human skin squamous cell carcinoma strongly overexpresses AQP3. A novel role for AQP3 in skin tumorigenesis was discovered using mice with targeted AQP3 gene disruption. We found that AQP3-null mice were remarkably resistant to the development of skin tumors following exposure to a tumor initiator and phorbol ester promoter. Though tumor initiator challenge produced comparable apoptotic responses in wild-type and AQP3-null mice, promoter-induced cell proliferation was greatly impaired in the AQP3-null epidermis. Reductions of epidermal cell glycerol, its metabolite glycerol-3-phosphate, and ATP were found in AQP3 deficiency without impairment of mitochondrial function. Glycerol supplementation corrected the reduced proliferation and ATP content in AQP3 deficiency, with cellular glycerol, ATP, and proliferative ability being closely correlated. Our data suggest involvement of AQP3-facilitated glycerol transport in epidermal cell proliferation and tumorigenesis by a novel mechanism implicating cellular glycerol as a key determinant of cellular ATP energy. AQP3 may thus be an important determinant in skin tumorigenesis and hence a novel target for tumor prevention and therapy.Skin cancer, including malignant melanoma, basal cell carcinoma, and squamous cell carcinoma (SCC), is the most common human cancer and represents a major public health concern due to its high incidence and the medical costs, mortality, and cosmetic associated deformities. A multistage skin tumor model has been used extensively to study the cellular, biochemical, and genetic events linked to the initiation, promotion, and progression steps of skin carcinogenesis (14, 29). The tumor induction protocol involves treatment with a single dose of the tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) followed by multiple applications of the tumor promoter 12-Otetradecanoylphorbol-13-acetate (TPA) (3,30). This leads to the development of papillomas, which are benign neoplastic lesions consisting of hyperplastic keratinocytes and supporting stromal cells.The aquaporins (AQPs) are a family of small, integral membrane proteins that transport water and in some cases small solutes, such as glycerol, termed aquaglyceroporins (AQPs 3, 7, and 9) (5, 27). Phenotype analysis of AQP knockout mice has revealed multiple roles for AQP-facilitated water transport in the urinary concentrating mechanism and in epithelial fluid secretion, brain edema, neural signal transduction, and cell migration (24, 28). In contrast, the aquaglyceroporins appear to be involved in metabolic pathways, such as adipose AQP7 in obesity (11, 12) and AQP9 in diabetes (22). The mechanisms underlying these phenomena were attributed to the glyceroltransporting function of aquaglyceroporins. In mammalian skin, AQP3 is expressed in plasma membranes of the basal epidermal cell layer (4,16,25). A human keratocarcinoma cell line has also been fo...

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“…Large islets with a high content of β-cells ( 90 % ; [16]) can be isolated, and the mitochondria obtained may be regarded to represent pure β-cells. Mitochondria were prepared as described in [17]. Comparative studies with mitochondria from lean mice demonstrated a normal function of ob\ob mice mitochondria [17].…”

Section: Isolation Of Mitochondriamentioning

confidence: 99%

Methyl pyruvate initiates membrane depolarization and insulin release by metabolic factors other than ATP

Lembert

Joos

Idahl

et al. 2001

Biochemical Journal

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The role of mitochondria in stimulus–secretion coupling of pancreatic β-cells was examined using methyl pyruvate (MP). MP stimulated insulin secretion in the absence of glucose, with maximal effect at 5mM. K+ (30mM) alone, or in combination with diazoxide (100µM), failed to enhance MP-induced secretion. Diazoxide (100µM) inhibited MP-induced insulin secretion. MP depolarized the β-cell in a concentration-dependent manner (5–20mM). The sustained depolarization induced by 20mM MP was not influenced by 100µM diazoxide, but the continuous spiking activity was suppressed by 500µM diazoxide. Pyruvate failed to initiate insulin release (5–20mM) or to depolarize the membrane potential. ATP production in isolated β-cell mitochondria was detected as accumulation of ATP in the medium during incubation in the presence of malate or glutamate in combination with pyruvate or MP. There was no difference in ATP production induced by pyruvate/malate or MP/malate in isolated β-cell mitochondria. ATP production by MP/glutamate was higher than that induced by pyruvate/glutamate, but it was much lower than that induced by α-ketoisocaproate/glutamate. Pyruvate (5mM) or MP (5mM) had no effect on the ATP/ADP ratio in whole islets, whereas glucose (20mM) significantly increased the whole islet ATP/ADP ratio. It is concluded that MP-induced β-cell membrane depolarization or insulin release does not relate directly to mitochondrial ATP production. Instead MP may exert a direct extramitochondrial effect, or it may stimulate β-cell mitochondria to produce coupling factors different from ATP to initiate insulin release.

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Glycerol 3-phosphate-induced ATP production in intact mitochondria from pancreatic B-cells

Cited by 34 publications

References 31 publications

The Pancreatic β-Cell: A Bioenergetic Perspective

The Pancreatic β-Cell: A Bioenergetic Perspective

Prevention of Skin Tumorigenesis and Impairment of Epidermal Cell Proliferation by Targeted Aquaporin-3 Gene Disruption

Methyl pyruvate initiates membrane depolarization and insulin release by metabolic factors other than ATP

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