Zachariah 2014 Diabetes: Difference between revisions
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{{Publication | {{Publication | ||
|title=Zachariah Tom | |title=Zachariah Tom R, Garcia-Roves PM, Sjögren RJ, Jiang LQ, Holmström MH, Deshmukh AS, Vieira E, Chibalin AV, Björnholm M, Zierath JR (2014) Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. Diabetes 63:1560-71. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24487023 PMID: 24487023] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/24487023 PMID: 24487023] | ||
|authors=Zachariah Tom | |authors=Zachariah Tom R, Garcia-Roves PM, Sjoegren RJ, Jiang LQ, Holmstroem MH, Deshmukh AS, Vieira E, Chibalin AV, Bjoernholm M, Zierath JR | ||
|year=2014 | |year=2014 | ||
|journal=Diabetes | |journal=Diabetes | ||
|abstract=AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation. | |abstract=AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation. | ||
|mipnetlab=ES Barcelona Garcia-Roves PM, SE Stockholm Morein T | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Genetic knockout;overexpression | |area=Respiration, Genetic knockout;overexpression | ||
|diseases=Diabetes, Obesity | |||
|organism=Mouse | |organism=Mouse | ||
|tissues=Skeletal muscle | |tissues=Skeletal muscle | ||
|preparations=Permeabilized tissue | |preparations=Permeabilized tissue | ||
|couplingstates=LEAK, OXPHOS, ET | |||
|couplingstates=LEAK, OXPHOS, | |pathways=N, NS | ||
| | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Latest revision as of 16:35, 13 November 2017
| Zachariah Tom R, Garcia-Roves PM, Sjögren RJ, Jiang LQ, Holmström MH, Deshmukh AS, Vieira E, Chibalin AV, Björnholm M, Zierath JR (2014) Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. Diabetes 63:1560-71. |
Zachariah Tom R, Garcia-Roves PM, Sjoegren RJ, Jiang LQ, Holmstroem MH, Deshmukh AS, Vieira E, Chibalin AV, Bjoernholm M, Zierath JR (2014) Diabetes
Abstract: AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation.
• O2k-Network Lab: ES Barcelona Garcia-Roves PM, SE Stockholm Morein T
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Diabetes, Obesity
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET
Pathway: N, NS
HRR: Oxygraph-2k
