Effect of Continuous GHRP-3 Infusion at on GH-IGF-I System, Blood Pressure, Glucose, and Insulin Resistance

At the lower dose of 0.1 µg/kg/h, GHRP-3 presumably will improve endothelial dysfunction,
enhance insulin action and lower blood pressure via the anti-inflammatory effects of GHRP-3
while at the higher dose of 0.5 µg/kg/h GHRP-3 these anti-inflammatory effects will be
further augmented by the hormonal action of increasing serum IGF-I and its primary serum
binding protein insulin like growth hormone binding protein - 3 (IGFBP-3 as well as -1).
Also, the more detailed inter-relationships between the actions of GHRP-3, GH and IGF-I on
serum glucose, blood pressure, and lipid levels over 24h periods will be determined at the
end of the 14 day placebo and two GHRP-3 infusion periods. The GHRP-3 will be administered
in escalating doses.

The Specific Aims of this study are as follows:

1. To determine the relative effects of 0.1µg/kg/h and 0.5µg/kg/h GHRP-3 as compared to
placebo infusion in inducing physiological secretion of the GH-IGF-I system after
continuous sc delivery for 14 days in healthy older men and women with insulin
resistance.

2. To determine the relative interrelated effects of 0.1 and 0.5µg/kg/h GHRP-3 infusion
and placebo on various hormonal and non hormonal aspects of insulin resistance such as
blood pressure (BP), plasma glucose and FFA as well as GH, IGF-I, IGFBP-1, -3, insulin
and endothelin-1 levels.

3. To determine the relative effects of placebo and the above 2 doses of GHRP-3 infusion
on flow mediated dilation (FMD) and nitroglycerin-dependent dilation