The role of increased lipid availability in the generation of insulin resistance by growth hormone has not been established. We investigated this in rats infused with saline (controls) or human growth hormone (hGH) (500 μg · kg− · 24 h−1) for 5 h or 3 days. hGH infusion increased basal plasma insulin at 5 h (335 ± 33 vs. 197 ± 15 [controls]; P < 0.005) and at 3 days (396 ± 34 vs. 218 ± 14 pmol/1; P < 0.0001). Plasma nonesterified fatty acid (0.26 ± 0.01 vs. 0.21 ± 0.01 [controls] g/l) and liver long-chain acyl-CoA (21.2 ± 1.9 vs. 14.1 ± 1.1 [controls] nmol/g wet wt) were elevated at 5 h (P < 0.01 for both) but were below control levels after 3 days of hGH infusion (P < 0.01 for both); indirect calorimetry after 3 days demonstrated decreased lipid oxidation. Clamp studies showed similar degrees of peripheral insulin resistance at 5-h and 3-day hGH infusion (glucose disposal reduced by 25% versus controls). Insulin-stimulated glucose metabolic index CRg′) in red gastrocnemius muscle (red muscle) was reduced (P < 0.05 and P < 0.01) at 5 h and 3 days of hGH infusion, respectively (e.g., 5 h, 10.0 ± 1.8 vs. 24.1 ± 4.4 [controls] μmol · 100 g−1 · min−1), whereas insulinmediated muscle glycogen synthesis was reduced (P < 0.03) only in rats infused with hGH for 3 days. We conclude that in the rat, hGH rapidly induces persistent peripheral insulin resistance and basal hyperinsulinemia. However, the transient nature of increased lipid mobilization suggests that it is not an important factor in the manifestation of muscle insulin resistance during prolonged hGH elevation. The persistent insulin resistance is not associated with increased lipid oxidation but is associated with hyperinsulinemia and reduced insulin-mediated muscle glycogen synthesis.
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Original Articles|
April 01 1996
Growth Hormone–Induced Insulin Resistance and Its Relationship to Lipid Availability in the Rat
Manthinda Hettiarachchi;
Manthinda Hettiarachchi
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Allan Watkinson;
Allan Watkinson
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Arthur B Jenkins;
Arthur B Jenkins
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Vicki Theos;
Vicki Theos
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Ken K Y Ho;
Ken K Y Ho
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Edward W Kraegen
Edward W Kraegen
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Address correspondence to Dr. Edward W. Kraegen, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria St., Darlinghurst, NSW 2010, Australia.
Diabetes 1996;45(4):415–421
Article history
Received:
March 09 1995
Revision Received:
November 16 1995
Accepted:
November 16 1995
PubMed:
8603761
Citation
Manthinda Hettiarachchi, Allan Watkinson, Arthur B Jenkins, Vicki Theos, Ken K Y Ho, Edward W Kraegen; Growth Hormone–Induced Insulin Resistance and Its Relationship to Lipid Availability in the Rat. Diabetes 1 April 1996; 45 (4): 415–421. https://doi.org/10.2337/diab.45.4.415
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