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AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • James Stoppani
  • Audrey L. Hildebrandt
  • Sakamoto, Kei
  • David Cameron-Smith
  • Laurie J. Goodyear
  • P. Darrell Neufer

AMP-activated protein kinase (AMPK) has recently emerged as a key signaling protein in skeletal muscle, coordinating the activation of both glucose and fatty acid metabolism in response to increased cellular energy demand. To determine whether AMPK signaling may also regulate gene transcription in muscle, rats were given a single subcutaneous injection (1 mg/g) of the AMP analog 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR). AICAR injection activated (P < 0.05) AMPK-α2 (∼2.5-fold) and transcription of the uncoupling protein-3 (UCP3, ∼4-fold) and hexokinase II (HKII, ∼10-fold) genes in both red and white skeletal muscle. However, AICAR injection also elicited (P < 0.05) an acute drop (60%) in blood glucose and a sustained (2-h) increase in blood lactate, prompting concern regarding the specificity of AICAR on transcription. To maximize AMPK activation in muscle while minimizing potential systemic counterregulatory responses, a single-leg arterial infusion technique was employed in fully conscious rats. Relative to saline-infused controls, single-leg arterial infusion of AICAR (0.125, 0.5, and 2.5 μg·g-1·min-1 for 60 min) induced a dose-dependent increase (2- to 4-fold, P < 0.05) in UCP3 and HKII transcription in both red and white skeletal muscle. Importantly, AICAR infusion activated transcription only in muscle from the infused leg and had no effect on blood glucose or lactate levels. These data provide evidence that AMPK signaling is linked to the transcriptional regulation of select metabolic genes in skeletal muscle.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology - Endocrinology and Metabolism
Vol/bind283
Udgave nummer6 46-6
Sider (fra-til)E1239-E1248
ISSN0193-1849
StatusUdgivet - 1 dec. 2002
Eksternt udgivetJa

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