Abstract
Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis.
Highlights
Diabetes is increasing worldwide [1] and is a known risk factor for cardiovascular disease, the leading cause of mortality in the U.S Low testosterone is associated with a greater risk for type 2 diabetes (T2D) in men [2,3,4,5]
Total fat mass was increased in male intrauterine growth-restricted offspring (mIUGR) and control offspring at 12 months relative to 6 months old groups. (Fig 1D).Lean mass per gram body weight was reduced in mIUGR and control offspring at 12 months old of age relative to control offspring at 6 months (Fig 1E) whereas fat mass per gram body weight was increased (Fig 1F)
Glucose intolerance was observed at 12 months of age in mIUGR relative to age-matched control
Summary
Diabetes is increasing worldwide [1] and is a known risk factor for cardiovascular disease, the leading cause of mortality in the U.S Low testosterone is associated with a greater risk for type 2 diabetes (T2D) in men [2,3,4,5]. A high endogenous level of free or total testosterone is associated with a lower fasting blood glucose and prevalence of T2D in men [6,7]. These studies indicate that testosterone deficiency in men is a risk factor for diabetes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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