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Glutamate is implicated in numerous metabolic and signalling functions that vary according to specific tissues. Glutamate metabolism is tightly controlled by activities of mitochondrial enzymes and transmembrane carriers, in particular glutamate dehydrogenase and mitochondrial glutamate carriers that have been identified in recent years. It is remarkable(More)
The SLC25 carrier family mediates solute transport across the inner mitochondrial membrane, a process that is still poorly characterized regarding both the mechanisms and proteins implicated. This study investigated mitochondrial glutamate carrier GC1 in insulin-secreting beta-cells. GC1 was cloned from insulin-secreting cells, and sequence analysis(More)
OBJECTIVE The reversible attachment of small ubiquitin-like modifier (SUMO) proteins controls target localization and function. We examined an acute role for the SUMOylation pathway in downstream events mediating insulin secretion. RESEARCH DESIGN AND METHODS We studied islets and β-cells from mice and human donors, as well as INS-1 832/13 cells. Insulin(More)
Pancreatic β-cells are poised to sense glucose and other nutrient secre-tagogues to regulate insulin exocytosis, thereby maintaining glucose homeostasis. This process requires translation of metabolic substrates into intracellular messengers recognized by the exocytotic machinery. Central to this metabolism-secretion coupling, mitochondria integrate and(More)
Pyruvate promotes hyperpolarization of the inner mitochondrial membrane. However, in isolated mitochondria, pyruvate could participate in a futile cycle leading to mitochondrial depolarization. Here, we investigated this paradox in intact human cells by measuring parameters reflecting mitochondrial activation in response to 1 mM pyruvate and 5 mM glucose.(More)
Transfer of reducing equivalents between cytosolic compartments and the mitochondrial matrix is mediated by NADH shuttles. Among these, the malate-aspartate shuttle has been proposed to play a major role in beta-cells for the control of glucose-stimulated insulin secretion. AGC1 or Aralar1 (aspartate-glutamate carrier 1) is a key component of the(More)
AIMS/HYPOTHESIS It is thought that the voltage-dependent potassium channel subunit Kv2.1 (Kv2.1) regulates insulin secretion by controlling beta cell electrical excitability. However, this role of Kv2.1 in human insulin secretion has been questioned. Interestingly, Kv2.1 can also regulate exocytosis through direct interaction of its C-terminus with the(More)
Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving as a junction between the extracellular matrix and actin cytoskeleton. Actin dynamics is known as a determinant step in insulin secretion. Additionally, FAK has been shown to regulate insulin signaling. To investigate the essential physiological role of FAK in pancreatic β-cells in(More)
Current notions about mechanisms by which catch-up growth predisposes to later type 2 diabetes center upon those that link hyperinsulinemia with an accelerated rate of fat deposition (catch-up fat). Using a rat model of semistarvation-refeeding in which catch-up fat is driven solely by elevated metabolic efficiency associated with hyperinsulinemia, we(More)
Sclerocarya birrea is a plant widely used as traditional medication for the treatment of diabetes in sub-Saharan regions. However, the mechanism of action is unknown and only hypoglycaemic effects of S. birrea extract (SBE) in diabetic rats have been reported to date. Here, we tested aqueous extracts of S. birrea on insulin-secreting INS-1E cells and(More)
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