Table 3:
Developmental Programming of Insulin Resistance by Gestational Androgen
| Animal Model | Insulin Resistance | Remarks | |
|---|---|---|---|
| Species | Treatment | ||
| Rhesus Macaques | Testosterone GD 40–80 (term 160) |
Yes |
Fetal: transient hyperglycemia and hyperinsulinemia (Abbott et al, 2010) Infants: increased basal insulin and beta cell number (Nicol et al, 2014) Adulthood: impaired disposition index, a measure of beta cell function and the ability to dispose glucose load (Eisner et al 2005) |
| Rhesus Macaques | Testosterone GD 100–115 (term 164) |
Yes | Impaired glucose tolerance in adulthood (Eisner et al, 2005) |
| Sheep (Suffolk) |
Testosterone GD 30–90 (term 147) |
Yes |
Juvenile period: decreased insulin sensitivity (Cardoso et al, 2016; Recabarren et al, 2005) Prepubertal period: decreased (Padmanabhan et al, 2010) or normal (Cardoso et al, 2016; Recabarren et al, 2005) insulin sensitivity based on proximity to puberty Postpubertal/ early adulthood: normal (Cardoso et al, 2016; Recabarren et al, 2005) or increased (Veiga-Lopez et al, 2013) insulin sensitivity Adulthood: Reduced insulin sensitivity (Padmanabhan et al, 2010) |
| Sheep (Suffolk) |
DHT GD 30–90 (term 147) |
Yes | Reduced insulin sensitivity at prepubertal age (Padmanabhan et al, 2010) |
| Sheep (Suffolk) |
Testosterone GD 60–90 (term 147) |
Yes | Reduced insulin sensitivity in adulthood (Padmanabhan et al, 2010) |
| Sheep (Scottish Greyface x Texel) |
Testosterone GD 62–102 (term 147) |
Yes | Adult age: normal glucose homeostasis but elevated basal insulin levels (Hogg et al, 2011) |
| Rat (Wister) |
Testosterone GD 20 (term 21) |
Yes | Single injection of testosterone during gestation impaired insulin sensitivity with normal HOMA index and glucose tolerance (Noroozzadeh et al, 2015) |
| Rat (Wistar) |
Testosterone GD 15–19 (term 21) |
Yes | Female offspring were insulin resistant compared male offspring, and this phenotype was prevented by flutamide or tamoxifen co-administration (Hu et al, 2015) |
| Rat (Sprague Dawley) | DHT GD 16–19 (term 21) |
Yes | Insulin resistance observed at pubertal age (Yan et al, 2013) |
| Rat (Wistar) |
Testosterone (5.0mg daily) GD 16–19 (term 21) |
No | Administration of 5 mg testosterone daily did not affect insulin sensitivity, but animals developed lipid disturbances and hepatic steatosis (Sun et al, 2012) |
| Rat (Sprague Dawley) | DHT Day 35–125 postnatal |
Yes | Hyperglycemia and hyperinsulinemia with increased body weight and perirenal fat at the end of the treatment period1 (Yanes et al, 2011) |
| Rat (Wistar) |
DHT Day 21–111 postnatal |
Yes | Decreased insulin sensitivity at the end of 90 day DHT treatment1 (Mannerås et al, 2007) |
| Rat (Wistar) |
Letrazole Day 21–111 postnatal |
No | No effect on insulin sensitivity at the end of 90 day DHT treatment (Mannerås et al, 2007) |
| Rat (Wistar) |
Estradiol Valerate Single injection Day 56 postnatal |
No | No change in insulin sensitivity or androgen levels (Stener-Victorin et al, 2005) |
| Rat (Sprague Dawley) | DHEA Day 21–41 postnatal |
Yes | Higher fasting glucose and insulin1 (Wang et al, 2004) |
| Rat (Sprague Dawley) | Testosterone Day 28–48 postnatal |
Yes | Hyperinsulinemia with reduced rate of glucose uptake1 (Holmäng et al, 1990) |
| Mouse (C57BL/N6) | Letrazole Day 28–88 postnatal |
Yes | Impaired glucose tolerance at unspecified age1 (Kauffman et al, 2015) |
| Mouse (C57Bl/6J) | DHT GD 16–18 (term 20) |
No | No effect on fasting glucose levels or insulin levels at 3 and 16 weeks of age (Caldwell et al, 2014) |
| Mouse (C57Bl/6J) | DHT Day 21–111 postnatal |
No | No effect on fasting glucose levels or insulin levels at 16 weeks of age1 (Caldwell et al, 2014) |
| Mouse (C57Bl/6J) | DHEA Day 21–111 postnatal |
No | No effect on fasting glucose levels or insulin levels at 16 weeks of age1 (Caldwell et al, 2014) |
| Mouse (C57Bl/6J) | Letrozole Day 21–111 postnatal |
No | No effect on fasting glucose levels or insulin levels at 16 weeks of age1 (Caldwell et al, 2014) |
| Mouse (C57Bl/6J) | DHT Day 19–109 postnatal |
Yes | Glucose intolerant at the end of a 90 day DHT treatment1 (van Houten et al, 2012) |
| Mouse (CBB6/F1) | DHT GD 16–18 (term 20) |
Yes | Prepuberty through adulthood: impaired glucose intolerance (Rolland et al, 2010) |
GD = gestational days; DHT = dihydrotestosterone; DHEA = Dehydroepiandrosterone;
1
Observations made either during treatment or end of treatment period – whether these effects are programmed or due to activational effects is not known.