Chronic β2 adrenergic agonist, but not exercise, improves glucose handling in older type 2 diabetic mice

Abstract

Insulin resistant type 2 diabetes mellitus in the obese elderly has become a worldwide epidemic. While exercise can prevent the onset of diabetes in young subjects its role in older diabetic people is less clear. Exercise stimulates the release of the β₂-agonist epinephrine more in the young. Although epinephrine and β₂-agonist drugs cause acute insulin resistance, their chronic effect on insulin sensitivity is unclear. We fed C57BL/6 mice a high fat diet to induce diabetes. These overweight animals became very insulin resistant. Exhaustive treadmill exercise 5 days a week for 8 weeks had no effect on their diabetes, nor did the β₂-blocking drug ICI 118551. In contrast, exercise combined with the β₂-agonist salbutamol (albuterol) had a beneficial effect on both glucose tolerance and insulin sensitivity after 4 and 8 weeks of exercise. The effect was durable and persisted 5 weeks after exercise and β₂-agonist had stopped. To test whether β₂-agonist alone was effective, the animals that had received β₂-blockade were then given β₂-agonist. Their response to a glucose challenge improved but their response to insulin was not significantly altered. The β₂-agonists are commonly used to treat asthma and asthmatics have an increased incidence of obesity and type 2 diabetes. Although β₂-agonists cause acute hyperglycemia, chronic treatment improves insulin sensitivity, probably by improving muscle glucose uptake.