A mechanistic examination of the metabolic regulation of insulin resistance, sarcopenia, and osteoporosis



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Aging is associated with a number of physiological changes, including increased risk of insulin resistance and type 2 diabetes mellitus (T2DM), decreased muscle mass and strength, and decreased bone mass and bone mineral density (BMD). The aim of the studies presented were to investigate 1) the kinetics of glucose-derived breath CO2 between drug naïve impaired glucose tolerant (IGT) and normal glucose tolerant (NGT) individuals following an oral glucose load, 2) the effects of chronic oral supplementation of essential amino acids (EAA) on the acute muscle protein synthetic response to an oral bolus of EAA in older men and women, and 3) the effects of continuous and monthly cycled administration of testosterone on markers of bone metabolism in older men with low normal endogenous testosterone production.\r\nStudy 1) During a 10-h oral glucose tolerance test, blood and breath samples were collected following ingestion of 75 g of glucose isotopically labeled with 150 mg of U-13C6-Glucose. Glucose-derived breath 13CO2 was lower in IGT as compared to NGT from 1 to 3.5 h post-glucose (P≤0.05). Glucose-derived breath CO2 kinetics measured during the immediate post-glucose ingestion period may assist in recognition of undiagnosed IGT in at-risk individuals during the pre-diabetes stage of T2DM.\r\nStudy 2) Older men and women received daily between-meal supplements of either 7.5 g EAA (LO), 15 g EAA (HI), or placebo (PL) for three months. Chronic EAA supplementation increased net phenylalanine uptake in the leg of LO and HI (P<0.05) without altering the magnitude of the acute FSR or total and phosphorylated Akt, mTOR, S6K1 or 4E-BP1 response. The magnitude of the anabolic response to an oral EAA ingestion in healthy older men and women remains intact after 3 months of EAA supplementation.\r\nStudy 3) Older men received continuous weekly testosterone injections for 5 months (TE), monthly cycled testosterone treatment (MO) or weekly placebo (PL). Continuous weekly testosterone administration resulted in decreased serum n-telopeptide (NTX) and serum osteocalcin (OC) in TE. Continuous testosterone treatment results in a decrease in both bone resorption and bone formation in older men.



muscle atrophy, glucose tolerance, bone loss, aging