Comparative Analysis of CTRP-Mediated Effects on Cardiomyocyte Glucose Metabolism: Cross Talk between AMPK and Akt

Ling Li1, Muhammad Aslam2, Benedikt H Siegler1

  • 1Institute of Physiology, Justus Liebig University Giessen, 35392 Giessen, Germany.

Cells
|April 30, 2021
PubMed

Insights

C1q/tumor necrosis factor-alpha-related proteins (CTRPs) influence heart cell metabolism. Specific CTRPs enhance glucose uptake via the AMPK pathway, offering potential therapeutic strategies for glucose homeostasis.

Area of Science:

  • Cardiovascular Biology
  • Metabolic Regulation
  • Cell Signaling

Background:

  • C1q/tumor necrosis factor-alpha-related proteins (CTRPs) are known for cardiovascular protection.
  • Their specific roles in cardiomyocyte glucose and fatty acid metabolism remain largely unexplored.

Purpose of the Study:

  • To investigate the effects of various CTRPs on glucose and fatty acid metabolism in cardiomyocytes.
  • To elucidate the involvement of AMP-activated protein kinase (AMPK) and Akt signaling pathways.

Main Methods:

  • Primary adult rat cardiomyocytes and H9C2 cardiomyoblasts were treated with recombinant CTRPs.
  • Glucose and fatty acid uptake, gene expression related to metabolism, and signaling pathway activation (AMPK, Akt) were assessed.
  • The role of adiponectin receptor 1 was examined.

Main Results:

  • CTRP2, 7, 9, and 13 significantly increased glucose uptake and GLUT1/GLUT4 translocation in cardiomyocytes.
  • These CTRPs modulated the expression of key metabolic enzymes.
  • AMPK activation was upstream of Akt activation in CTRP signaling.
  • Adiponectin receptor 1 partially mediated CTRP effects on glucose metabolism.

Conclusions:

  • Specific CTRPs (CTRP2, 7, 9, 13) enhance cardiomyocyte glucose uptake through AMPK-dependent signaling.
  • Targeting the AMPK pathway with CTRPs presents a potential therapeutic approach for improving glucose homeostasis.

Related Concept Videos

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,...
7.2K
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
282
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...
4.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.3K
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...
4.0K