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 JT; Veldhuis. Johannes D JD; Tena-Sempere. Manuel M; Millar. Robert P RP; Anderson. Richard A RA
Key Findings
- IV kisspeptin‑10 quickly doubled LH levels in both healthy and diabetic men
- A prolonged IV infusion of kisspeptin‑10 increased testosterone from ~8.5 to ~11.4 nmol/L in diabetic men
- LH pulse frequency and overall LH secretion rose during the infusion, indicating enhanced hypothalamic‑pituitary activity
Practical Outcomes
- While the results hint that kisspeptin agonists could become a new way to boost natural testosterone in men with diabetes‑related hypogonadism, the study used intravenous delivery and a very small sample, so it isn’t ready for DIY use. More research is needed to develop safe, practical dosing forms (e.g., oral or sub‑cutaneous) before biohackers can consider it a viable protocol.
Summary
In a tiny study, giving men with type‑2 diabetes and low testosterone a short burst of the hormone‑like peptide kisspeptin‑10 raised their luteinising hormone (LH) and, after a longer infusion, also lifted their testosterone levels. The effect was seen both in healthy volunteers and the diabetic participants, showing kisspeptin can kick‑start the body’s own testosterone production, but the work was done with IV doses and involved only a handful of people.
Abstract
Low serum testosterone is commonly observed in men with type 2 diabetes (T2DM), but the neuroendocrine pathophysiology remains to be elucidated. 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. 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, HbA1c 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). 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.
Study Information
pubmed
2013
2013-04-19T00:00:00.000Z
10.1111/cen.12103
121
17