Mechanisms of dexamethasone-induced insulin resistance in healthy humans.
Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour. During the second hour, glucose uptake was normalized by means of hyperglycemia; glucose oxidation, however, remained suppressed by dexamethasone. Dexamethasone also abolished the insulin-mediated increase in calf blood flow. When acipimox was administered during the clamps to correct glucocorticoid-induced inhibition of glucose oxidation, dexamethasone decreased whole body glucose uptake and nonoxidative glucose disposal in the same proportion as when no acipimox was administered. However, glucose oxidation and insulin-mediated calf blood flow were normalized after acipimox. During the second hour, exogenous glucose infusion was matched to that used in the control clamp and normalized whole body glucose uptake. However, hyperglycemia developed, indicating insulin resistance. It is concluded that dexamethasone 1) decreases glucose oxidation independently of glucose transport; this inhibition is reversed by acipimox; and 2) decreases whole body glucose uptake independently of increased lipolysis, decreased glucose oxidation, or an altered muscle blood flow.
Tappy
L
L
Institute of Physiology, University of Lausanne, Switzerland.
Randin
D
D
Vollenweider
P
P
Vollenweider
L
L
Paquot
N
N
Scherrer
U
U
Schneiter
P
P
Nicod
P
P
Jéquier
E
E
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007866:Leg / Q000098:blood supply; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects
D001786:Blood Glucose; D000960:Hypolipidemic Agents; D007328:Insulin; D011719:Pyrazines; D003907:Dexamethasone; D005947:Glucose; C027696:acipimox