Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics.
The ability of growth hormone (GH) to stimulate lipolysis and cause insulin resistance in skeletal muscle may be causally linked, but the mechanisms remain obscure. We investigated the impact of GH on the turnover of FFA and VLDL-TG, intramuscular triglyceride content (IMTG), and insulin sensitivity (euglycemic clamp) in nine healthy men in a randomized double-blind placebo-controlled crossover study after 8 days treatment with (A) Placebo+Placebo, (B) GH (2 mg daily)+Placebo, and (C) GH (2 mg daily)+Acipimox (250 mgx3 daily). In the basal state, GH (B) increased FFA levels (P<0.05), palmitate turnover (P<0.05), and lipid oxidation (P=0.05), but VLDL-TG kinetics were unaffected. Administration of acipimox (C) suppressed basal lipolysis but did not influence VLDL-TG kinetics. In the basal state, IMTG content increased after GH (B; P=0.03). Insulin resistance was induced by GH irrespective of concomitant acipimox (P<0.001). The turnover of FFA and VLDL-TG was suppressed by hyperinsulinemia during placebo and GH, whereas coadministration of acipimox induced a rebound increase FFA turnover and VLDL-TG clearance. We conclude that these results show that GH-induced insulin resistance is associated with increased IMTG and unaltered VLDL-TG kinetics; we hypothesize that fat oxidation in muscle tissue is an important primary effect of GH and that circulating FFA rather than VLDL-TG constitute the major source for this process; and the role of IMTG in the development of GH-induced insulin resistance merits future research.
Krag
Morten B
MB
Medical Department M, Endocrinology and Diabetes, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Gormsen
Lars C
LC
Guo
Zengkui
Z
Christiansen
Jens S
JS
Jensen
Michael D
MD
Nielsen
Søren
S
Jørgensen
Jens O L
JO
D000328:Adult; D001835:Body Weight / Q000187:drug effects; D002153:Calorimetry, Indirect; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D010919:Placebos; D014280:Triglycerides / Q000032:analysis* / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D010919:Placebos; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose