AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle.

This research investigates how administering AICAR, a molecule that activates certain metabolic pathways, affects the body’s glucose metabolism in horses. The study reveals a potential role for AICAR in managing Equine Metabolic Syndrome, a disease akin to human Type 2 diabetes.

Background

• Equine metabolic syndrome is a common health issue in horses, characterized by obesity and insulin resistance. As yet, there is no effective pharmacological treatment.
• Glucose uptake, vital for energy production, is mediated by a family of proteins known as glucose transporters (GLUT).
• This process is controlled by both insulin-dependent and independent pathways. One such insulin-independent pathway involves the 5-AMP-activated protein kinase (AMPK).
• Previous studies have shown that activation of AMPK by a drug known as 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in humans, both healthy and diabetic.
• The researchers hypothesize that AICAR administration could enhance glucose transport in equine skeletal muscle through AMPK activation.

Methodology

• The researchers administered an intravenous AICAR infusion to horses and measured consequent changes in blood glucose and insulin concentrations, along with alterations in the expression of GLUT proteins and activation of AMPK, in skeletal muscle tissue.

Results

• AICAR caused a rapid peak in its plasma concentration post-administration.
• A decrease in blood glucose and an increase in insulin concentration was observed in the horses after the drug treatment. Lactate concentration, however, remained unchanged.
• The AMPK activation in skeletal muscle tissue was increased following AICAR treatment.
• While expressions of GLUT4 and GLUT1 proteins remained unchanged, there was a noticeable increase in GLUT8 protein expression after AICAR treatment.

Significance

• The study suggests an important role for the newly discovered glucose transporter, GLUT8, in regulating glucose transport in equine muscle.
• The surge in insulin concentration after AICAR treatment may indicate that AMPK activation enhances pancreatic insulin secretion.
• The research points to the therapeutic potential of AICAR in managing insulin resistance, thus opening up a new avenue for pharmacological intervention in equine metabolic syndrome.