Effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle.

The research investigates the effects of a steroid medication, dexamethasone, on insulin resistance in horses, showing that prolonged dexamethasone treatment can result in significant insulin resistance and alter specific components of the insulin signaling pathway.

Research Objective

• This study sought to understand the effects of administering dexamethasone on components related to insulin signaling and glucose metabolism in horse muscle tissues. By analyzing muscle biopsy specimens before and after the administration of a euglycemic-hyperinsulinemic clamp (EHC), the researchers aimed at providing conclusive findings on how dexamethasone affects insulin resistance.

Methods

• The research involved a balanced crossover study on six adult Standardbreds. Horses received either dexamethasone or a saline solution intravenously for 21 days.
• The EHC, a technique meanwhile offering a constant insulin and glucose level in the bloodstream, was used for the measurement of insulin sensitivity the day after treatment.
• Horses’ muscle biopsy specimens were collected before and after the EHC administration to check various factors of glucose metabolism. These included glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3alpha/beta protein abundance, phosphorylation state, glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration.

Findings

• Dexamethasone treatment led to a resting hyperinsulinemia (excessive insulin level in the blood) in horses and a marked 70% decrease in glucose infusion rate during the EHC, indicating increased insulin resistance.
• In the group treated with dexamethasone, an increase in the hexokinase enzyme activity, inhibition of the insulin-stimulated rise in glycogen synthase, and decreased phosphorylation of GSK-3alpha Ser(21) and GSK-3B Ser(9) were observed.
• However, dexamethasone did not impact the content of the glucose transporter 4 or glycogen concentration, and it did not affect PKB abundance and phosphorylation state.

Conclusion

• The research concluded that 21 days of dexamethasone treatment in horses led to considerable insulin resistance and affected GSK-3 phosphorylation in skeletal muscle in a way that it could reduce glycogen synthase activity after insulin stimulation.