Increased lipid oxidation but normal muscle glycogen response to epinephrine in humans with IDDM.
The effects of physiological increments in epinephrine and insulin on glucose production (GP), skeletal muscle glycogen metabolism, and substrate oxidation were studied in eight insulin-dependent diabetes mellitus (IDDM) and nine control subjects. Epinephrine was coinfused for the final 120 min of a 240-min euglycemic, hyperinsulinemic clamp. In both groups, insulin increased glucose uptake, glycogen synthesis, and whole body carbohydrate (CHO) oxidation and inhibited GP (by 70-80%) and lipid oxidation (by approximately 50%), whereas epinephrine antagonized the effect of insulin on glucose uptake and glycogen synthesis. In contrast, GP increased in IDDM subjects (P < 0.02) but remained suppressed by insulin in controls. CHO oxidation fell (1.37 +/- 0.25 vs. 2.08 +/- 0.32 mg.kg-1.min-1) and lipid oxidation increased to baseline in IDDM subjects, with increments in plasma free fatty acids (FFA) and glycerol. In contrast, in controls, plasma FFA and glycerol remained suppressed and lipid oxidation decreased further with epinephrine (P < 0.005). Epinephrine completely reversed insulin's activation of muscle glycogen synthase in both groups. Thus, during hyperinsulinemia, the hepatic response to epinephrine in IDDM subjects may be dependent on activation of lipid oxidation. Skeletal muscle glycogen metabolism is exquisitely sensitive to epinephrine despite the presence of hyperinsulinemia.
Cohen
N
N
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Halberstam
M
M
Rossetti
L
L
Shamoon
H
H
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D006005:Phosphorylases / Q000378:metabolism; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D006728:Hormones; D007328:Insulin; D006003:Glycogen; D006005:Phosphorylases; D006006:Glycogen Synthase; D004837:Epinephrine