title: 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 β(2)-agonist epinephrine more in the young. Although epinephrine and β(2)-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 β(2)-blocking drug ICI 118551. In contrast, exercise combined with the β(2)-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 β(2)-agonist had stopped. To test whether β(2)-agonist alone was effective, the animals that had received β(2)-blockade were then given β(2)-agonist. Their response to a glucose challenge improved but their response to insulin was not significantly altered. The β(2)-agonists are commonly used to treat asthma and asthmatics have an increased incidence of obesity and type 2 diabetes. Although β(2)-agonists cause acute hyperglycemia, chronic treatment improves insulin sensitivity, probably by improving muscle glucose uptake.
authors.affiliation: Department of Pharmacology, The University of Jordan, Amman, Jordan.
authors.forename: Hamzeh
authors.initials: H
authors.lastname: Elayan
authors.forename: Milos
authors.initials: M
authors.lastname: Milic
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Munir
authors.initials: M
authors.lastname: Gharaibeh
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ziegler
mesh_terms: D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects*; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal
chemical_list: D000322:Adrenergic Agonists; D001786:Blood Glucose; D000420:Albuterol