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 and whether there are age-specific differences in the regulation of ghrelin. Insulin sensitivity decreases with age. The studies proposed will investigate whether there are differences between young and older adults regarding the acute insulin mediated decrease in circulating ghrelin (bioactive, inactive form) levels. We hypothesize that insulin administered under euglycemic conditions will decrease ghrelin to a lesser extent in older adults when compared to young adults. Insulin administered under euglycemic conditions will decrease circulating ghrelin levels to the same extent in older adults as in young adults when matched for BMI, waist circumference and insulin sensitivity. For this purpose, 24 men and women (12 of each gender) age 60 years and older will be recruited. The volunteers have 2 admissions. There is a euglycemic hyperinsulinemic clamp admission and a control admission which has a saline instead of an insulin infusion. The insulin-induced suppression of acyl-and desacyl-ghrelin will be compared to a group of young men and women recruited and tested under another protocol. Using assays developed in the investigators'laboratory, both bioactive and inactive ghrelin will be measured.
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