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- W2029371986 abstract "AMP-activated protein kinase (AMPK) has recently been implicated in the control of preproinsulin gene expression in pancreatic islet β-cells [da Silva Xavier, Leclerc, Salt, Doiron, Hardie, Kahn and Rutter (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 4023–4028]. Using pharmacological and molecular strategies to regulate AMPK activity in rat islets and clonal MIN6 β-cells, we show here that the effects of AMPK are exerted largely upstream of insulin release. Thus forced increases in AMPK activity achieved pharmacologically with 5-amino-4-imidazolecarboxamide riboside (AICAR), or by adenoviral overexpression of a truncated, constitutively active form of the enzyme (AMPKα1.T172D), blocked glucose-stimulated insulin secretion. In MIN6 cells, activation of AMPK suppressed glucose metabolism, as assessed by changes in total, cytosolic or mitochondrial [ATP] and NAD(P)H, and reduced increases in intracellular [Ca2+] caused by either glucose or tolbutamide. By contrast, inactivation of AMPK by expression of a dominant-negative form of the enzyme mutated in the catalytic site (AMPKα1.D157A) did not affect glucose-stimulated increases in [ATP], NAD(P)H or intracellular [Ca2+], but led to the unregulated release of insulin. These results indicate that inhibition of AMPK by glucose is essential for the activation of insulin secretion by the sugar, and may contribute to the transcriptional stimulation of the preproinsulin gene. Modulation of AMPK activity in the β-cell may thus represent a novel therapeutic strategy for the treatment of type 2 diabetes mellitus." @default.
- W2029371986 created "2016-06-24" @default.
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- W2029371986 date "2003-05-01" @default.
- W2029371986 modified "2023-09-23" @default.
- W2029371986 title "Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression" @default.
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- W2029371986 cites W1972762474 @default.
- W2029371986 cites W1976261899 @default.
- W2029371986 cites W1981668713 @default.
- W2029371986 cites W1983844571 @default.
- W2029371986 cites W1987787422 @default.
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- W2029371986 cites W2000659699 @default.
- W2029371986 cites W2000795392 @default.
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- W2029371986 cites W2016944998 @default.
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- W2029371986 cites W2028754125 @default.
- W2029371986 cites W2029121966 @default.
- W2029371986 cites W2033823674 @default.
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- W2029371986 cites W2036784822 @default.
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- W2029371986 cites W2067511291 @default.
- W2029371986 cites W2068245283 @default.
- W2029371986 cites W2069978422 @default.
- W2029371986 cites W2076927702 @default.
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- W2029371986 doi "https://doi.org/10.1042/bj20021812" @default.
- W2029371986 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1223356" @default.
- W2029371986 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12589707" @default.
- W2029371986 hasPublicationYear "2003" @default.
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