Related Experiment Video

Updated: Dec 10, 2025

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
08:01

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice

Published on: May 16, 2021

6.4K

AKT2 regulates development and metabolic homeostasis via AMPK-depedent pathway in skeletal muscle

Miao Chen1, Caoyu Ji2, Qingchen Yang2

  • 1State Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, China.

Clinical Science (London, England : 1979)
|September 4, 2020
PubMed

Insights

This study reveals that AKT2 deficiency impairs skeletal muscle development and glucose metabolism by down-regulating AMP-activated protein kinase (AMPK) signaling. Restoring AMPK activity can reverse these detrimental effects in AKT2 knockout mice.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Skeletal muscle is crucial for glucose disposal, and its insulin resistance significantly impacts type 2 diabetes (T2D).
  • The precise mechanisms underlying skeletal muscle insulin resistance in T2D remain incompletely understood.
  • AKT2 plays a role in cellular processes, but its specific function in skeletal muscle development and metabolism requires further elucidation.

Purpose of the Study:

  • To investigate the role of AKT2 in skeletal muscle development and metabolism.
  • To determine if AKT2 deficiency leads to deficits in glucose uptake and utilization in skeletal muscle.
  • To explore the underlying molecular mechanisms, particularly the involvement of AMP-activated protein kinase (AMPK) signaling.

Main Methods:

  • Analysis of gene and protein expression in AKT2 knockout (KO) and wild-type (WT) mice at 3 and 8 months of age.
  • Assessment of molecules involved in skeletal muscle development, glucose uptake, and metabolism.
  • Investigation of the effects of AMP-activated protein kinase (AMPK) activation on molecular pathways in AKT2 KO mice.
  • Evaluation of AMPK signaling in response to insulin stimulation.

Main Results:

  • AKT2 deficiency resulted in down-regulated AMP-activated protein kinase (AMPK) phosphorylation and myocyte enhancer factor 2 A (MEF2A) expression.
  • Reduced mitochondrial DNA (mtDNA) abundance and impaired mitochondrial biogenesis gene expression were observed in AKT2 KO mice.
  • AMPK activation reversed the observed deficits in AMPK phosphorylation, MEF2A expression, and mitochondrial parameters.
  • AKT2 KO mice showed impaired AMPK signaling in response to insulin stimulation compared to WT mice.

Conclusions:

  • AKT2 plays a critical role in regulating skeletal muscle development and glucose metabolism.
  • The function of AKT2 in skeletal muscle is mediated through AMP-activated protein kinase (AMPK)-dependent signaling pathways.
  • These findings highlight AKT2 as a potential therapeutic target for improving skeletal muscle function and glucose homeostasis in metabolic diseases like T2D.
Keywords:
AKT2AMPKglucose metabolismmitochondriaskeletal muscle

More Related Videos

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

19.5K
Isolation and Differentiation of Primary Myoblasts from Mouse Skeletal Muscle Explants06:53

Isolation and Differentiation of Primary Myoblasts from Mouse Skeletal Muscle Explants

Published on: October 15, 2019

18.2K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.0K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.5K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
9.8K
Regulation of Metabolism01:19

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
11.0K