![]() ![]() The shuttle is composed of two enzymatic functions present both in the cytosol and mitochondrial matrix (AAT and MDH), and two transporters located in the inner mitochondrial membrane (AGC and OGC). The MAS translocates electrons produced during glycolysis across the inner mitochondrial membrane for oxidative phosphorylation. Accordingly, pyruvate- and lactate-elicited glucagon secretion remains unaffected since their signalling is independent of mitochondrial shuttles.The malate-aspartate shuttle (MAS) and its specific metabolic functions in the CNS and liver, respectively. Thus, suppressed glycerol phosphate shuttle activity in the α-cell may prevent a high rate of glycolysis and consequently glucagon secretion in response to glucose. Furthermore, expression of the rate-limiting enzyme of the glycerol phosphate shuttle was higher in sorted primary β- than in α-cells. These results were confirmed in mouse islets, where PhS abrogated secretion of glucagon but not insulin. Our data suggest that the glycerol phosphate shuttle augments the malate–aspartate shuttle in INS-1 832/13 but not αTC1-6 cells. Accordingly, relative expression of constituents in the glycerol phosphate shuttle compared with malate–aspartate shuttle was lower in αTC1-6 cells. Blocking the malate–aspartate shuttle increased levels of glycerol 3-phosphate only in INS-1 832/13 cells. Inhibition of the malate–aspartate shuttle, using phenyl succinate (PhS), abolished glucose-provoked ATP production and hormone secretion from αTC1-6 but not INS-1 832/13 cells. Although glycolytic metabolism was similar in the two cell lines, TCA (tricarboxylic acid) cycle metabolism, respiration and ATP levels were less glucose-responsive in αTC1-6 cells. In contrast, tight coupling of glycolytic and mitochondrial metabolism was observed only in INS-1 832/13 cells. We found that INS-1 832/13 and αTC1-6 cells respectively secreted insulin and glucagon concentration-dependently in response to glucose. Therefore, we studied the regulation of glucagon secretion from αTC1-6 (αTC1 clone 6) cells and compared it with insulin release from INS-1 832/13 cells. Access content during the Covid-19 pandemicĪltered secretion of insulin as well as glucagon has been implicated in the pathogenesis of Type 2 diabetes (T2D), but the mechanisms controlling glucagon secretion from α-cells largely remain unresolved. ![]()
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