Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity.
Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, and body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (approximately 55 mU/L) clamp in conjunction with paired muscle biopsies for measurement of glycogen synthase fractional velocity (FV0.1). Despite similar basal rates of total glucose disposal (Rd), there was a 64% reduction in the insulin-stimulated rise (delta) in Rd in the GHD adults compared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mumol/kg fat free mass (FFM)/min; P < 0.001], which was mainly due to a decreased glucose storage (GS) rate (delta GS, 12.6 +/- 2.9 vs. 39.5 +/- 7.5 mumol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexes of Rd (0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS (0.25 +/- 0.07 vs. 0.72 +/- 0.13 mumol/kg FFM/min per mU/L; P < 0.02) were reduced in GHD adults compared to the control values. The insulin sensitivity of the glycolytic pathway was also reduced by approximately 50% in GHD adults (P = 0.07 vs. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite similar basal FV0.1. Using multiple and stepwise regression analysis, duration of GH deficiency, fasting triglycerides and fasting insulin accounted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly due to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficiency, fasting triglycerides, and fasting insulin.
Hew
F L
FL
Department of Endocrinology and Diabetes, St. Vincent's Hospital, Fitzroy, Melbourne, Victoria, Australia.
Koschmann
M
M
Christopher
M
M
Rantzau
C
C
Vaag
A
A
Ward
G
G
Beck-Nielsen
H
H
Alford
F
F
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001824:Body Constitution; D015992:Body Mass Index; D005215:Fasting; D005260:Female; D006006:Glycogen Synthase / Q000378:metabolism*; D013006:Growth Hormone / Q000172:deficiency*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000201:enzymology; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D013006:Growth Hormone; D006006:Glycogen Synthase