Ghrelin is a novel gastric peptide which stimulates growth hormone and has orexigenic and adipogenic properties. Plasma ghrelin is influenced by nutritional status and is thought to play a role in regulating food intake and body weight. We examined the effect of infusing insulin (40 mU/m(2)/min) for 2 hours while maintaining euglycemia on plasma ghrelin in 8 subjects (5 M, 3 F) aged 46 +/- 4 yrs (mean +/- SEM). Plasma insulin increased from 78 +/- 9 to 564 +/- 23 pmol/L during and returned rapidly to basal values after stopping the insulin infusion. Plasma ghrelin decreased from 85 +/- 28 to 61 +/- 18 pmol/L (p < 0.01) by 90 minutes of and continued to be suppressed for 15 minutes after the insulin infusion was discontinued. Subsequently, plasma ghrelin rose rapidly to near-basal values (81 +/- 23 pmol/L) within 60 minutes. The reciprocal relation between insulin and ghrelin was observed consistently in all subjects with the maximum insulin-induced suppression of ghrelin ranging from 19 to 64% (mean 32 +/- 5) and occurring 90-135 minutes after starting the insulin infusion (median 120). These findings indicate that insulin is a physiological and dynamic modulator of plasma ghrelin and that insulinemia possibly mediates the effect of nutritional status on its concentration.
Continuous glucose monitoring has the potential to improve glucose management and reduce the risk of hypoglycemia in individuals with diabetes. Accurate sensors may also allow the development of a closed-loop insulin delivery system. The purpose of this work was to determine the delay time associated with a subcutaneous glucose sensor during rapidly changing glucose excursions. Subcutaneous glucose sensors (Medtronic MiniMed, Inc., Northridge, CA) were inserted in five healthy men. After a 2-h stabilization period, a 3-h hyperglycemic (approximately 11 mM) clamp was performed followed by a 90-min period in which plasma glucose was allowed to decline to as low as 2.8 mM. Sensors were calibrated using two points (basal and hyperglycemia), and the calibrated sensor glucose measurements were compared with those from a reference analyzer (Beckman Instruments, Fullerton, CA). Response time was estimated from a first-order kinetic model. Plasma glucose levels, determined with the subcutaneous sensor, were highly correlated with those obtained with the reference glucose analyzer (r(2) = 0.91, p < 0.001; mean absolute difference of approximately 8%). The half-time for the sensor response was estimated to be 4.0 +/- 1.0 min. The subcutaneous glucose sensor has the potential to facilitate the detection of hypoglycemia and improve overall glycemic control when used in a real-time monitor. The rapid response should be sufficient to allow a fully automated closed-loop insulin delivery system to be developed based on the subcutaneous sensing site.
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