SUN-LB62 Differential Regulation of 22 kDa and 20 kDa Growth Hormone Isoforms in Response to Acute Glucose Load and Moderate Intensity Exercise

Background: Among growth hormone (GH) isoforms, the 22kDa (22kD) is the most abundant (~90%), followed by 20 kDa GH ((20kD) ~10%). 22kD has known diabetogenic potential by increasing insulin resistance. Although of equal somatotropic activity, 20kD has been suggested to be less diabetogenic. Under physiological conditions, both isoforms are largely secreted in parallel, but data on regulation of both isoforms in the context of glucose load and utilization are scarce. Methods: We measured 20- and 22kD GH in fasted healthy adult females during two scenarios: (A) Premenopausal females (n = 25; age (mean (range)) 27.8 (22-52), body mass index (BMI) (kg/m(2)) 21.8 (18.2-27.3), insulin sensitivity index (ISI) 7.9 (3.2-19.7) underwent an oral glucose tolerance test (OGTT, 75g, sampling at baseline, 30, 60, 90, 120 and 180 minutes (min); (B) Premenopausal females within 1 year postpartum (n=28, age 36 (29-44), BMI 23.7 (19.4-41.3), ISI (7.2- (2.4-13.2)) performed moderate intensity exercise (fixed workload 60% VO(2)max, sampling at -15, -10, -5, 0, 3, 6, 10, 15, 20, 30 and 45 min and after 5, 10 and 15 min of resting). 20- and 22kD were measured by specific immunoassays (22kD: IDS-iSYS GH CLIA, limit of quantification (LoQ) 0.05 ng/mL; 20kD: in-house immunofluorometric assay (IFMA), LoQ 0.025 ng/mL), and the 20/22kD ratio was calculated. Results: As expected, both, 22kD and 20kD concentrations decreased after glucose load. However, the 20/22kD ratio increased significantly (Friedman test, P = 0.04, Kendall’s W 0.69, Conover’s post test: 0 vs. 60, 90 and 120 min; P = 0.018, 0.032 and 0.018, respectively. After 120 min, 20/22kD returned to baseline. With exercise, both, 20- and 22kD increased. In contrast to glucose load, the 20/22kD ratio significantly decreased (Friedman test, P = 0.025, Kendall’s W 0.59, Conover’s post test: -10 vs. 10 and 20 min; P = 0.015 and 0.022, respectively), reaching a nadir at 10 min and returning to the baseline after cessation of exercise (20 vs. 50, 55 and 60 min; P = 0.02, 0.005 and 0.016, respectively. Conclusion: Glucose load and exercise lead to opposite changes in the 20/22kD ratio, suggesting a tight regulation by glucose demands. We speculate that the putative less diabetogenic isoform (20kD) is preferentially secreted during situations of glucose excess, while the opposite happens during exercise, when increased energy demands are associated with predominant upregulation of the more diabetogenic 22kD GH.