AMP-activated protein kinase and the metabolic syndrome.

@article{Fryer2005AMPactivatedPK,
  title={AMP-activated protein kinase and the metabolic syndrome.},
  author={Lee G. D. Fryer and David Carling},
  journal={Biochemical Society transactions},
  year={2005},
  volume={33 Pt 2},
  pages={
          362-6
        }
}
  • L. Fryer, D. Carling
  • Published 1 April 2005
  • Biology, Medicine
  • Biochemical Society transactions
The occurrence of Type II (non-insulin-dependent) diabetes and obesity and their associated morbidities continue to increase and they are rapidly reaching epidemic proportions. AMPK (AMP-activated protein kinase) was initially thought of as an intracellular 'fuel gauge' responding to a decrease in the level of ATP by increasing energy production and decreasing energy utilization. Recent studies have shown that AMPK plays a role in controlling the whole body energy homoeostasis, including the… 
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It seems possible that AMPK or one of its effectors is a positive regulator of insulin-stimulated glucose transport, and this review includes a non-technical summary for students, academics from other fields, interested professionals, and the general public.
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Data reveal a new role for AMPKα2 subunit in the regulation of cardiac muscle oxidative capacity via cardiolipin homeostasis as well as a new target to treat metabolic disorders.
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The dynamic change of blood glucose, represented in a form of initiative increase and subsequent decrease in the early stage of sepsis, may be related to glycometabolism disorder in the skeletal muscle, coming down to enhancement of GLUT4 translocation expression promoted by activation of AMPKα.
Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis in Diabetic LDL Receptor–Deficient Mice
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It is revealed that inactivation of hepatic AMPK is a key event in the pathogenesis of hyperlipidemia in diabetes, point to a novel mechanism of action of polyphenols to lower lipids by activating AMPK, and emphasize a new therapeutic avenue to benefit hyper Lipidemia and atherosclerosis specifically in diabetes.
Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States
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It is suggested that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.
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Attempts to solve the crystal structures of dimeric human IR kinase domains and complexes of these with IR agonists failed, but biophysical characterization of the full-length intracellular part of the IR containing the kinase domain demonstrated an intrinsic ability to dimerize independently of the enzyme-substrate type of interaction seen in IR autophosphorylation.
AMP-activated protein kinase : Screening for novel membrane substrates and creatine kinase phosphorylation linked to specific subcellular compartment
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The results suggest that AMPK seems to regulate more probably the association of BCK to subcellular compartments and not enzyme activity, which may support heavily ATP-dependent processes in this microenvironment like e.g. calcium pumping.
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References

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TLDR
It is demonstrated that counter-regulatory hormones involved in appetite control regulate AMPK activity and that pharmacological activation of AMPK in the hypothalamus increases food intake, and that AMPK is identified as a novel target for anti-obesity drugs.
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
TLDR
Hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance, and inhibition of hypothalamic AM PK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects.
C75, a Fatty Acid Synthase Inhibitor, Reduces Food Intake via Hypothalamic AMP-activated Protein Kinase*
TLDR
Modulation of FAS activity in the hypothalamus can alter energy perception via AMPK, which functions as a physiological energy sensor in the amygdala, which regulates feeding behavior and mediates the anorexic effects of C75.
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TLDR
The results suggest that the increase in lipid storage in adipose tissue in AMPKalpha2 KO mice may have protected these mice from further impairment of glucose homeostasis that normally accompanies high-fat feeding.
The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity.
AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the…
The Anti-diabetic Drugs Rosiglitazone and Metformin Stimulate AMP-activated Protein Kinase through Distinct Signaling Pathways*
TLDR
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  • D. Carling
  • Biology, Medicine
    Trends in biochemical sciences
  • 2004
AMPK β Subunit Targets Metabolic Stress Sensing to Glycogen
The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism.
TLDR
Evidence is presented that activation of AMPK in two different cell types is not a consequence of depletion of cellular energy charge via this mechanism, and the mechanism is different from that of the existing AMPK-activating agent, 5-aminoimidazole-4-carboxamide (AICA) riboside.
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TLDR
It is found that ATP depletion was accelerated in transgenic mice with cardiac-specific overexpression of a dominant negative mutant of the AMPK α2 catalytic subunit during no-flow ischemia, and these hearts developed left ventricular dysfunction manifested by an early and more rapid increase inleft ventricular end-diastolic pressure.
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