Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea

Stimulation of AMP-activated protein kinase (AMPK) in skeletal muscle has been correlated with an increase in glucose transport. Here, we demonstrate that adenoviral-mediated expression of a constitutively active mutant of AMPKα leads to activation of glucose transport in a skeletal-muscle cell line, similar to that seen following treatment with 5-amino-imidazolecarboxamide (AICA) riboside, hyperosmotic stress or insulin. In contrast, expression of a dominant-negative form of AMPK blocked the stimulation of glucose transport by both AICA riboside and hyperosmotic stress, but was without effect on either insulin or phorbol-ester-stimulated transport. These results demonstrate that activation of AMPK is sufficient for stimulation of glucose uptake into muscle cells, and is a necessary component of the AICA riboside- and hyperosmotic-stress-induced pathway leading to increased glucose uptake. On the other hand, AMPK is not required in the insulin- or phorbol-ester-mediated pathways. Long-term (5 days) expression of the constitutively active AMPK mutant increased protein expression of GLUT1, GLUT4 and hexokinase II, consistent with previous reports on the chronic treatment of rats with AICA riboside. Expression of constitutively active AMPK had no detectable effect on p38 mitogen-activated protein kinase levels, although interestingly the level of protein kinase B was decreased. These results demonstrate that long-term activation of AMPK is sufficient to cause increased expression of specific proteins in muscle. Our results add further support to the hypothesis that long-term activation of AMPK is involved in the adaptive response of muscle to exercise training.

Download Full-text

CAPE (caffeic acid phenethyl ester) stimulates glucose uptake through AMPK (AMP-activated protein kinase) activation in skeletal muscle cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2007.07.068 ◽

2007 ◽

Vol 361 (4) ◽

pp. 854-858 ◽

Cited By ~ 58

Author(s):

Eun Soo Lee ◽

Kyung-Ok Uhm ◽

Yun Mi Lee ◽

MyungSuk Han ◽

MyungSik Lee ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Glucose Uptake ◽

Caffeic Acid ◽

Muscle Cells ◽

Caffeic Acid Phenethyl Ester ◽

Skeletal Muscle Cells ◽

Kinase Activation ◽

Protein Kinase Activation ◽

Amp Activated Protein Kinase

Download Full-text

Antihypertensive peptide purified from Styela clava flesh tissue stimulates glucose uptake through AMP-activated protein kinase (AMPK) activation in skeletal muscle cells

European Food Research and Technology ◽

10.1007/s00217-015-2526-7 ◽

2015 ◽

Vol 242 (2) ◽

pp. 163-170 ◽

Cited By ~ 5

Author(s):

Seok-Chun Ko ◽

Jae-Il Kim ◽

Sun-Joo Park ◽

Won-Kyo Jung ◽

You-Jin Jeon

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Glucose Uptake ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Ampk Activation ◽

Styela Clava ◽

Amp Activated Protein Kinase

Download Full-text

Diphenylene iodonium stimulates glucose uptake in skeletal muscle cells through mitochondrial complex I inhibition and activation of AMP-activated protein kinase

Cellular Signalling ◽

10.1016/j.cellsig.2007.02.006 ◽

2007 ◽

Vol 19 (7) ◽

pp. 1610-1620 ◽

Cited By ~ 33

Author(s):

Dana S. Hutchinson ◽

Robert I. Csikasz ◽

Daniel L. Yamamoto ◽

Irina G. Shabalina ◽

Per Wikström ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Glucose Uptake ◽

Complex I ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

Diphenylene Iodonium ◽

Amp Activated Protein Kinase

Download Full-text

Rapid stimulation of glucose transport by mitochondrial uncoupling depends in part on cytosolic Ca2+ and cPKC

AJP Cell Physiology ◽

10.1152/ajpcell.1998.275.6.c1487 ◽

1998 ◽

Vol 275 (6) ◽

pp. C1487-C1497 ◽

Cited By ~ 61

Author(s):

Zayna A. Khayat ◽

Theodoros Tsakiridis ◽

Atsunori Ueyama ◽

Romel Somwar ◽

Yousuke Ebina ◽

...

Keyword(s):

Plasma Membrane ◽

Protein Kinase ◽

Glucose Uptake ◽

Glucose Transport ◽

Energy Demand ◽

Plasma Membranes ◽

Muscle Cells ◽

Atp Production ◽

Pkc Β ◽

Stimulation Of

2,4-Dinitrophenol (DNP) uncouples the mitochondrial oxidative chain from ATP production, preventing oxidative metabolism. The consequent increase in energy demand is, however, contested by cells increasing glucose uptake to produce ATP via glycolysis. In L6 skeletal muscle cells, DNP rapidly doubles glucose transport, reminiscent of the effect of insulin. However, glucose transport stimulation by DNP does not require insulin receptor substrate-1 phosphorylation and is wortmannin insensitive. We report here that, unlike insulin, DNP does not activate phosphatidylinositol 3-kinase, protein kinase B/Akt, or p70 S6 kinase. However, chelation of intra- and extracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM in conjunction with EGTA inhibited DNP-stimulated glucose uptake by 78.9 ± 3.5%. Because Ca2+-sensitive, conventional protein kinase C (cPKC) can activate glucose transport in L6 muscle cells, we examined whether cPKC may be translocated and activated in response to DNP in L6 myotubes. Acute DNP treatment led to translocation of cPKCs to plasma membrane. cPKC immunoprecipitated from plasma membranes exhibited a twofold increase in kinase activity in response to DNP. Overnight treatment with 4-phorbol 12-myristate 13-acetate downregulated cPKC isoforms α, β, and γ and partially inhibited (45.0 ± 3.6%) DNP- but not insulin-stimulated glucose uptake. Consistent with this, the PKC inhibitor bisindolylmaleimide I blocked PKC enzyme activity at the plasma membrane (100%) and inhibited DNP-stimulated 2-[3H]deoxyglucose uptake (61.2 ± 2.4%) with no effect on the stimulation of glucose transport by insulin. Finally, the selective PKC-β inhibitor LY-379196 partially inhibited DNP effects on glucose uptake (66.7 ± 1.6%). The results suggest interfering with mitochondrial ATP production acts on a signal transduction pathway independent from that of insulin and partly mediated by Ca2+ and cPKCs, of which PKC-β likely plays a significant role.

Download Full-text