THE IMPACT OF INSULIN ON THE SHORT-TERM REGULATION OF GHRELIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ghrelin, a peptide which is mainly derived from the stomach, is present in plasma in an active (acylated) and inactive (des-acylated) form. The major active form of ghrelin contains 28 amino acids with a unique post-translational modification: the hydroxyl group of ser3 is esterified by octanoic acid. The n-octanoyl group is essential for the growth hormone (GH) releasing activity. Plasma ghrelin plays a role in energy homeostasis, food intake, and possibly in GH release and obesity. To date, it is unclear how circulating ghrelin levels are regulated. Studies of insulin effects on ghrelin levels under euglycemic conditions have yielded inconsistent results, i.e., a decrease in circulating ghrelin vs. no change. It is also unclear whether differences in insulin resistance have an impact on the effects of insulin and/or glucose on circulating ghrelin. We will examine the effects of insulin under euglycemic conditions on peripheral ghrelin in two groups of BMI matched young adults with different insulin resistance. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured. For this purpose, twenty-four young women (n=12 in low insulin resistance group, n=12 in high insulin resistance group) and 24 young men (n=12 in low insulin resistance group, n=12 in high insulin resistance group), (ages 18-30 yrs) will be studied in a single-blind placebo-controlled experiment (BMI 18.5 to 35 kg/m2). The volunteers have 3 admissions. There are two euglycemic hyperinsulinemic clamp admissions (with 2 different insulin infusion rates: 0.4 mU/kg/min and 1 mU/kg/min) and one control admission which has a saline instead of an insulin infusion. The insulin induced suppression of acyl-and desacyl-ghrelin will be compared after the two groups have been matched for BMI. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured.