ArticleThe Journal of biological chemistry2012
Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 99 citations in OpenAlex.
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- The Use of Ceramides to Predict Metabolic Response to Metformin in Women With PCOS.Journal of the Endocrine Society · 2022Article
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- A novel phenolic formulation for treating hepatic and peripheral insulin resistance by regulating GLUT4-mediated glucose uptake.Journal of traditional and complementary medicine · 2022Article
- Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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- Glucose Uptake and Insulin Response in Tissue-engineered Human Skeletal Muscle.Tissue engineering and regenerative medicine · 2020Article
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- Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism.American journal of physiology. Cell physiology · 2020Article
- SHIPping out diabetes-Metformin, an old friend among new SHIP2 inhibitors.Acta physiologica (Oxford, England) · 2020Review
- Prenatal metformin exposure or organic cation transporter 3 knock-out curbs social interaction preference in male mice.Pharmacological research · 2019Article
- Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The importance of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) as effectors of metformin (Met) action on glucose uptake (GU) in skeletal muscle cells was investigated. GU in L6 myotubes was stimulated 2-fold following 16 h of Met treatment and acutely enhanced by insulin in an additive fashion. Insulin-stimulated GU was sensitive to PI3K inhibition, whereas that induced by Met was not. Met and its related biguanide, phenformin, stimulated AMPK activation/phosphorylation to a level comparable with that induced by the AMPK activator, 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (AICAR). However, the increase in GU elicited by AICAR was significantly lower than that induced by either biguanide. Expression of a constitutively active AMPK mimicked the effects of AICAR on GU, whereas a dominant interfering AMPK or shRNA silencing of AMPK prevented AICAR-stimulated GU and Met-induced AMPK signaling but only repressed biguanide-stimulated GU by ∼20%. Consistent with this, analysis of GU in muscle cells from α1(-/-)/α2(-/-) AMPK-deficient mice revealed a significant retention of Met-stimulated GU, being reduced by ∼35% compared with that of wild type cells. Atypical PKCs (aPKCs) have been implicated in Met-stimulated GU, and in line with this, Met and phenformin induced activation/phosphorylation of aPKC in L6 myotubes. However, although cellular depletion of aPKC (>90%) led to loss in biguanide-induced aPKC phosphorylation, it had no effect on Met-stimulated GU, whereas inhibitors targeting novel/conventional PKCs caused a significant reduction in biguanide-induced GU. Our findings indicate that although Met activates AMPK, a significant component of Met-stimulated GU in muscle cells is mediated via an AMPK-independent mechanism that involves novel/conventional PKCs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.