Endocrine Abstracts

Gestational diabetes (GDM) occurs when beta-cell insulin secretory capacity is insufficient to meet the increased demands required to maintain normoglycemia during pregnancy. Considerable clinical evidence supports a link between depression and GDM, although underlying mechanisms are unclear. We used the unpredictable chronic mild stress (UCMS) rodent model of depression to examine the metabolic effects of depression in pregnant mice. C57BL/6J females were divided at 4-weeks-old into control or UCMS-treated groups. UCMS-treated mice were singly-housed and subjected daily to multiple stressors for 6-weeks, whilst controls were pair-housed under normal conditions. Sucralose preference testing showed UCMS mice had reduced sucralose preference, indicative of increased anhedonia (72.6±0.7% vs Control 83.4±0.65% P <0.0001). UCMS mice exhibited depressive-like behaviours in both Porsolt Swim and Splash tests, with decreased latency to immobility (81±6s vs Control 129±19s P = 0.02) and increased latency to grooming (121±15s vs Control 75±11s P = 0.02), respectively. Whilst baseline plasma corticosterone levels were indistiguishable between groups (P = 0.98), the increase in costicosterone in response to the Porsolt test was significantly reduced in UCMS mice (78.2±7.6ng/ml vs Control 107.5±6.2ng/ml P = 0.0005). Mice underwent intraperitoneal glucose tolerance (IPGTT) and insulin tolerance (IPITT) tests, both before pregnancy and at gestational days 16-18 of pregnancy. Non-pregnant UCMS females showed a trend for improved glucose tolerance (1452±46 AUC vs Control 1590±56 P = 0.07), whilst pregnant UCMS females had significantly improved glucose tolerance (1616±97 AUC vs Control 2051±188 P = 0.05). There were no changes in insulin sensitivity (non-pregnant P = 0.96, pregnant P = 0.15) or plasma insulin levels (non-pregnant P = 0.26, pregnant P = 0.52) between groups. In conclusion, UCMS provides a good depression model in C57BL/6J females, with increased anhedonia, behavioural despair and a blunted HPA-axis stress-response. However, rather than correlating with impaired glucose tolerance, our study suggested depression produced a protective metabolic phenotype, improving glucose homeostasis, independently of insulin sensitivity.