Growth hormone deficiency (GHD) in adults seems to predispose to insulin resistance (IR). Development of GHD related IR could be associated with adipose tissue (AT) derived signals. To investigate the nature of this pathological regulation we 1) measured gene expressions for leptin, adiponectin, TNFalpha, IL-6, 11beta HSD1, SREBP, PPARgamma in the AT of untreated GHD adults, and 2) assessed effect of euglycemic hyperinsulinemia (HI) at the gene level.
Methods: 17 patients (9M/8F) aged 2141 yrs with GH deficiency were studied. Controls (C) were matched with patients for BMI, age and sex. Subcutaneous (s.c.) AT biopsies were performed once after overnight fast before an oGTT, and 2nd time in the 3rd hr of an euglycemic HI clamp. mRNA levels were assessed using real-time RT-PCR.
Results: Compared to the matched controls, the GHD subjects did not differ in the in vivo insulin action and triglyceride levels. In the basal state GHD patients had raised RNA levels for leptin (P<0.001), TNFalpha (P<0.05) and SREBP (P<0.05) as well as for IL-6 (P<0.05) and 11beta HSD-1 (P<0.05). In both groups, euglycemic HI led to elevation of mRNA for SREBP (P<0.001) and PPAR gamma (P<0.05). Gene expression for leptin increased further in the GHD patients only.
Conclusions: 1) The whole body insulin-induced glucose utilization of GHD patients was not altered when compared to BMI, age and sex matched controls; 2) nevertheless, GHD patients had already raised s.c. AT gene expression for lipostatic /leptin/, proinflammatory /TNFalpha, IL-6/ and proadipogenic /11beta HSD-1, SREBP/ pathways in basal state, and 3) euglycemic HI increased gene expression for leptin only. Thus, changes in s.c. AT at the gene level are present in GHD subjects with features of the metabolic syndrome who seem not to be IR due to a GH deficit.
Supported by STAA No. 51-0406/02.
01 - 05 Apr 2006
European Society of Endocrinology