A New Role for Pancreatic Insulin in the Male Reproductive Axis

  1. Mary R. Loeken
  1. Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts
  1. Corresponding author: Mary R. Loeken, mary.loeken{at}joslin.harvard.edu.

The recent discovery that insulin is expressed by the rat testis (1) raises questions about whether and how locally produced insulin regulates testicular function. It also raises the question whether pancreatic insulin regulates testicular function, and whether fertility might be impaired as a consequence of insulin deficiency in type 1 diabetes. As reported in this issue of Diabetes, Schoeller et al. (2) have found that pancreatic insulin regulates the male hypothalamic-pituitary-gonadal axis and is essential for fertility. In contrast, insulin produced in the testes may not be essential for testicular function. The article by Schoeller et al. provides an important advance toward understanding why fertility may be diminished in men with type 1 diabetes.

It has only recently been recognized that diabetes can reduce sperm quality and that the female partners of diabetic men have lower pregnancy rates (3,4). It is not well understood whether hyperglycemia or abnormal insulin signaling is responsible, and what stage(s) of spermatogenesis is affected. Increased nuclear and mitochondrial DNA damage in sperm samples from diabetic men suggests that hyperglycemia-induced oxidative stress may be responsible (3,5). However, it is also possible that the adverse effects of diabetes may be due to abnormal insulin signaling in the testis, systemic effects of insulin, or both, and may be separate from insulin’s effects on blood glucose levels.

Schoeller et al. (2) have taken advantage of …

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