Search

The majority of insulin-like growth factor-I (IGF-I) in the adult rodent circulation is bound to high affinity IGF binding proteins. We investigated the changes in IGF-I clearance, blood glucose and plasma insulin levels, and tissue 2-deoxyglucose uptake after intravenous administration of the IGF aptamer, NBI-31772, which selectively competes with IGF-I for binding to the IGFBPs, but has no effect at the IGF-I receptor. Clearance of 125I-IGF-I was significantly increased in NBI-31772-treated mice compared with vehicle-treated mice (t1/2 = 45.0 +/- 1.9 vs. 56.3 +/- 3.9 min, respectively; p = 0.021). However, NBI-31772 had no significant effect on glucose levels, and no insulin sparing effect was apparent neither under basal conditions nor during an intravenous glucose challenge. The decline in the specific activity after 3H-2-deoxyglucose administration was significantly less rapid in NBI-31772-treated mice compared with controls, suggesting that the IGF-I aptamer had an inhibitory effect on hepatic gluconeogenesis. In contrast, no insulin-like effect was apparent in other tissues examined. 3H-2-deoxyglucose accumulation was similar in all tissues analyzed, including skeletal muscle, which is thought to be particularly sensitive to IGF-I. These data suggest that the IGF-I aptamer affects clearance of radiolabeled IGF-I from the circulation, but has no marked effects on glucose nor insulin homeostasis. The search for hydrophilic IGF aptamers with longer duration of action that could be used in the treatment of diabetes may be rewarding.

Summary background Insulin resistance, impaired glucose tolerance and type 2 diabetes are common in acromegalic subjects. The mechanism underlying this insulin resistance is unclear. design We investigated the levels of the adipocytokines, resistin, adiponectin and leptin in a group of 18 acromegalic subjects and 18 control subjects matched for age, gender and body mass index. results Here we demonstrate for the first time significant elevation in adiponectin levels in acromegalic subjects compared to control subjects 12·5 ± 1·2 vs. 8·97 ± 1·1 mg/l, P = 0·029. The resistin levels were similar in acromegalic subjects and controls; 20·65 ± 2·99 vs. 19·03 ± 4·72 µg/l. No evidence of a correlation between adiponectin and insulin resistance as calculated from HOMA-R was found. No correlation was observed either between adiponectin or resistin levels and GH levels, total IGF-I or free IGF-I levels. Leptin levels were significantly reduced in acromegalic subjects, 8·22 ± 2·26 vs. 18·3 ± 4·1 µg/l, P = 0·004. In control subjects, significant correlations between leptin levels and HOMA-R and between resistin levels and HOMA-R were observed. These relationships were not apparent in acromegalic subjects. conclusion From these data we conclude that changes in resistin and adiponectin levels are unlikely to account for the insulin resistance of acromegaly. [ABSTRACT FROM AUTHOR]