Tags

Type your tag names separated by a space and hit enter

Physiologic concentrations of exogenously infused ghrelin reduces insulin secretion without affecting insulin sensitivity in healthy humans.
J Clin Endocrinol Metab. 2013 Jun; 98(6):2536-43.JC

Abstract

BACKGROUND

Infusion of ghrelin to supraphysiologic levels inhibits glucose-stimulated insulin secretion, reduces insulin sensitivity, and worsens glucose tolerance in humans.

OBJECTIVE

The purpose of this study was to determine the effects of lower doses of ghrelin on insulin secretion and insulin sensitivity in healthy men and women.

METHODS

Acyl ghrelin (0.2 and 0.6 nmol kg(-1) h(-1)) or saline was infused for 225 minutes in 16 healthy subjects on 3 separate occasions in randomized order. An i.v. glucose tolerance test was performed, and the insulin sensitivity index (SI) was derived from the minimal model. Insulin secretion was measured as the acute insulin response to glucose (AIRg) and the disposition index was computed as AIRg × SI.

RESULTS

Ghrelin infusions at 0.2 and 0.6 nmol kg(-1) h(-1) raised steady-state plasma total ghrelin levels 2.2- and 6.1-fold above fasting concentrations. Neither dose of ghrelin altered fasting plasma insulin, glucose, or SI, but both doses reduced insulin secretion compared with the saline control, computed either as AIRg (384 ± 75 and 354 ± 65 vs 520 ± 110 pM · min [mean ± SEM], respectively; P < .01 for both low- and high-dose vs saline) or disposition index (2238 ± 421 and 2067 ± 396 vs 3339 ± 705, respectively; P < .02 for both comparisons). The high-dose ghrelin infusion also decreased glucose tolerance.

CONCLUSIONS

Ghrelin infused to levels occurring in physiologic states such as starvation decreases insulin secretion without affecting insulin sensitivity. These findings are consistent with a role for endogenous ghrelin in the regulation of insulin secretion and suggest that ghrelin antagonism could improve β-cell function.

Authors+Show Affiliations

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA. jenny.tong@uc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23589527

Citation

Tong, Jenny, et al. "Physiologic Concentrations of Exogenously Infused Ghrelin Reduces Insulin Secretion Without Affecting Insulin Sensitivity in Healthy Humans." The Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 6, 2013, pp. 2536-43.
Tong J, Prigeon RL, Davis HW, et al. Physiologic concentrations of exogenously infused ghrelin reduces insulin secretion without affecting insulin sensitivity in healthy humans. J Clin Endocrinol Metab. 2013;98(6):2536-43.
Tong, J., Prigeon, R. L., Davis, H. W., Bidlingmaier, M., Tschöp, M. H., & D'Alessio, D. (2013). Physiologic concentrations of exogenously infused ghrelin reduces insulin secretion without affecting insulin sensitivity in healthy humans. The Journal of Clinical Endocrinology and Metabolism, 98(6), 2536-43. https://doi.org/10.1210/jc.2012-4162
Tong J, et al. Physiologic Concentrations of Exogenously Infused Ghrelin Reduces Insulin Secretion Without Affecting Insulin Sensitivity in Healthy Humans. J Clin Endocrinol Metab. 2013;98(6):2536-43. PubMed PMID: 23589527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physiologic concentrations of exogenously infused ghrelin reduces insulin secretion without affecting insulin sensitivity in healthy humans. AU - Tong,Jenny, AU - Prigeon,Ronald L, AU - Davis,Harold W, AU - Bidlingmaier,Martin, AU - Tschöp,Matthias H, AU - D'Alessio,David, Y1 - 2013/04/15/ PY - 2013/4/17/entrez PY - 2013/4/17/pubmed PY - 2013/8/10/medline SP - 2536 EP - 43 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 98 IS - 6 N2 - BACKGROUND: Infusion of ghrelin to supraphysiologic levels inhibits glucose-stimulated insulin secretion, reduces insulin sensitivity, and worsens glucose tolerance in humans. OBJECTIVE: The purpose of this study was to determine the effects of lower doses of ghrelin on insulin secretion and insulin sensitivity in healthy men and women. METHODS: Acyl ghrelin (0.2 and 0.6 nmol kg(-1) h(-1)) or saline was infused for 225 minutes in 16 healthy subjects on 3 separate occasions in randomized order. An i.v. glucose tolerance test was performed, and the insulin sensitivity index (SI) was derived from the minimal model. Insulin secretion was measured as the acute insulin response to glucose (AIRg) and the disposition index was computed as AIRg × SI. RESULTS: Ghrelin infusions at 0.2 and 0.6 nmol kg(-1) h(-1) raised steady-state plasma total ghrelin levels 2.2- and 6.1-fold above fasting concentrations. Neither dose of ghrelin altered fasting plasma insulin, glucose, or SI, but both doses reduced insulin secretion compared with the saline control, computed either as AIRg (384 ± 75 and 354 ± 65 vs 520 ± 110 pM · min [mean ± SEM], respectively; P < .01 for both low- and high-dose vs saline) or disposition index (2238 ± 421 and 2067 ± 396 vs 3339 ± 705, respectively; P < .02 for both comparisons). The high-dose ghrelin infusion also decreased glucose tolerance. CONCLUSIONS: Ghrelin infused to levels occurring in physiologic states such as starvation decreases insulin secretion without affecting insulin sensitivity. These findings are consistent with a role for endogenous ghrelin in the regulation of insulin secretion and suggest that ghrelin antagonism could improve β-cell function. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/23589527/Physiologic_concentrations_of_exogenously_infused_ghrelin_reduces_insulin_secretion_without_affecting_insulin_sensitivity_in_healthy_humans_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2012-4162 DB - PRIME DP - Unbound Medicine ER -