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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
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
Clinical Endocrinology, Volume 79, No. 1, Year 2013
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Description
Rationale Low serum testosterone is commonly observed in men with type 2 diabetes (T2DM), 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 T2DM. Participants Five hypotestosteronaemic men with T2DM (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 T2DM (4·7 ± 0·7 to 10·7 ± 1·2 IU/l P = 0·02) with comparable ΔLH (P = 0·18). Experiment 2 Baseline 10-min serum sampling for LH and hourly testosterone measurements were performed in four T2DM 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 T2DM 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 T2DM and central hypogonadism. © 2012 John Wiley & Sons Ltd.
Authors & Co-Authors
George, Jyothis T.
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Veldhuis, Johannes D.
United States, Rochester
Mayo Clinic
Tena-Sempere, Manuel
Spain, Cordoba
Universidad de Córdoba
Millar, Robert P.
South Africa, Cape Town
University of Cape Town
South Africa, Pretoria
University of Pretoria
United Kingdom, Edinburgh
The University of Edinburgh
Anderson, Richard A.A.
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Statistics
Citations: 114
Authors: 5
Affiliations: 6
Identifiers
Doi:
10.1111/cen.12103
ISSN:
03000664
e-ISSN:
13652265
Research Areas
Noncommunicable Diseases
Sexual And Reproductive Health
Study Approach
Quantitative
Participants Gender
Male