AMPK: Cellular Energy Sensor

AMPK (AMP-activated protein kinase) is a universal cellular energy sensor. Activated when the AMP/ATP ratio increases (low cellular energy, fasting, exercise), it stimulates catabolic pathways (fat oxidation, glucose uptake) and inhibits anabolic pathways (cholesterol synthesis, lipogenesis). It is the target of metformin, the primary treatment for type 2 diabetes.

Characteristics

• Heterotrimeric αβγ
• Activated by: low ATP, exercise, hypoxia, fasting
• Pharmacological activators: metformin, AICAR, A-769662
• Natural activators: [6]-gingerol, curcumin, resveratrol, EGCG, berberine

Effects of AMPK activation

• ↑ Muscle glucose uptake (insulin-independent)
• ↓ Hepatic glucose production
• ↑ Fatty acid oxidation
• ↓ Cholesterol synthesis and lipogenesis
• ↑ Cellular autophagy (waste elimination)
• ↓ mTOR (longevity)
• ↓ Systemic inflammation

AMPK and longevity

Chronic AMPK activation is associated with increased longevity in many animal models. It is one of the pathways activated by caloric restriction, intermittent fasting, and exercise.

AMPK and diabetes

In T2 diabetes, AMPK is under-activated. Metformin activates AMPK, and this is its main mechanism of action. [6]-gingerol also activates AMPK (Phytomedicine 2018 study) — hence its interest in diabetes.

Documented natural activators

• [6]-gingerol: comparable AMPK activation (but weaker) to metformin
• Curcumin + piperine: AMPK activation + improved insulin sensitivity
• Berberine: very powerful, sometimes called "natural metformin"
• Resveratrol, EGCG, fisetin

AMPK and INTI

The ginger + turmeric + piperine combination from INTI activates AMPK through several mechanisms. Interesting for: T2 diabetes, prediabetes, metabolic syndrome, longevity, weight loss.