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Cited by 105

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: Kisspeptin‐10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism

George, Jyothis T., Veldhuis, Johannes D., Tena‐Sempere, Manuel, Millar, Robert P., Anderson, Richard A.·2013·Clinical Endocrinology
DOI 10.1111/cen.12103
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Abstract

Rationale: Low serum testosterone is commonly observed in men with type 2 diabetes (T2 DM), but the neuroendocrine pathophysiology remains to be elucidated. Objectives: The hypothalamic neuropeptide kisspeptin integrates metabolic signals with the reproductive axis in animal models. We hypothesized that administration of exogenous kisspeptin‐10 will restore luteinizing hormone (LH) and testosterone secretion in hypotestosteronaemic men with T2 DM. Participants: Five hypotestosteronaemic men with T2 DM (age 33·6 ± 3 years, BMI 40·6 ± 6·3, total testosterone 8·5 ± 1·0 nmol/l, LH 4·7 ± 0·7 IU/l, HbA 1c 7·4±2%, duration of diabetes <5 years) and seven age‐matched healthy men. Experiment 1: Mean LH increased in response to intravenous administration of kisspeptin‐10 (0·3 mcg/kg bolus) both in healthy men (5·5 ± 0·8 to 13·9 ± 1·7 IU/l P < 0·001) and in men with T2 DM (4·7 ± 0·7 to 10·7 ± 1·2 IU/l P = 0·02) with comparable Δ LH (P = 0·18). Experiment 2: Baseline 10‐min serum sampling for LH and hourly testosterone measurements were performed in four T2 DM men over 12 h. An intravenous infusion of kisspeptin‐10 (4 mcg/kg/h) was administered for 11 h, 5 days later. There were increases in LH (3·9 ± 0·1 IU/l to 20·7 ± 1·1 IU/l P = 0·03) and testosterone (8·5 ± 1·0 to 11·4 ± 0·9 nmol/l, P = 0·002). LH pulse frequency increased from 0·6 ± 0·1 to 0·9 ± 0 pulses/h (P = 0·05) and pulsatile component of LH secretion from 32·1 ± 8·0 IU/l to 140·2 ± 23·0 IU/l (P = 0·007). Conclusions: Kisspeptin‐10 administration increased LH pulse frequency and LH secretion in hypotestosteronaemic men with T2 DM in this proof‐of‐concept study, with associated increases in serum testosterone. These data suggest a potential novel therapeutic role for kisspeptin agonists in enhancing endogenous testosterone secretion in men with T2 DM and central hypogonadism.

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Research works printed but not linked: 12

  1. 10.1210/jc.2004-0804 · DOI · Paper page
  2. 10.1159/000299767 · DOI
  3. 10.1210/er.2003-0002 · DOI
  4. 10.1159/000314193 · DOI
  5. 10.2337/db05-1584 · DOI
  6. 10.1007/BF03345620 · DOI
  7. 10.1210/en.2004-0413 · DOI · Paper page
  8. 10.1210/jc.2011-0089 · DOI · Paper page
  9. 10.1152/ajpendo.00071.2009 · DOI · Paper page
  10. 10.1210/jc.85.12.4500 · DOI
  11. 10.1152/ajpregu.00314.2012 · DOI
  12. 10.1210/en.2012-1429 · DOI

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Metadata

Authors
George, J. T., Veldhuis, J. D., Tena‐Sempere, M., Millar, R. P., & Anderson, R. A.
Affiliations
  • MRC Centre for Reproductive Health The Queen's Medical Research Institute University of Edinburgh Edinburgh EH16 4TJ UK
  • Endocrine Research Unit Center for Translational Science Activities Mayo Clinic Rochester Minnesota USA
  • Department of Cell Biology Physiology and Immunology &amp; CIBER Fisiopatologia de la Obesidad y Nutrición University of Cordoba 14004 Cordoba Spain
  • MRC/UCT Receptor Biology and Reproductive Health Group Division of Medical Biochemistry University of Cape Town Observatory 7925 South Africa
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2013-04-19
Volume
79
Issue
1
Pages
100-104
ISSN
  • 0300-0664
  • 1365-2265
DOI
10.1111/cen.12103
Cited by
105
References
5
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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