کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1948317 1537491 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Studies with leucine, β-hydroxybutyrate and ATP citrate lyase-deficient beta cells support the acetoacetate pathway of insulin secretion
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Studies with leucine, β-hydroxybutyrate and ATP citrate lyase-deficient beta cells support the acetoacetate pathway of insulin secretion
چکیده انگلیسی

We hypothesized that contrasting leucine with its non-metabolizable analog 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) might provide new information about metabolic pathways involved in insulin secretion. Both compounds stimulate insulin secretion by allosterically activating glutamate dehydrogenase, which enhances glutamate metabolism. However, we found that leucine was a stronger secretagogue in rat pancreatic islets and INS-1 cells. This suggested that leucine's metabolism contributed to its insulinotropism. Indeed, we found that leucine increased acetoacetate and was metabolized to CO2 in pancreatic islets and increased short chain acyl-CoAs (SC-CoAs) in INS-1 cells. We then used the leucine–BCH difference to study the hypothesis that acyl groups derived from secretagogue carbon can be transferred as acetoacetate, in addition to citrate, from mitochondria to the cytosol where they can be converted to SC-CoAs. Since BCH cannot form sufficient acetoacetate from glutamate, transport of any glutamate-derived acyl groups to the cytosol in BCH-stimulated cells must proceed mainly via citrate. In ATP citrate lyase-deficient INS-1 cells, which are unable to convert citrate into cytosolic acetyl-CoA, insulin release by BCH was decreased and adding β-hydroxybutyrate or α-ketoisocaproate, which increases mitochondrial acetoacetate, normalized BCH-induced insulin release. This strengthens the concept that acetoacetate-transferred acyl carbon can be converted to cytosolic SC-CoAs to stimulate insulin secretion.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - General Subjects - Volume 1780, Issues 7–8, July–August 2008, Pages 966–972
نویسندگان
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