Selective estrogen receptor modulation in pancreatic β-cells and the prevention of type 2 diabetes

Tiano, Joseph P.; Mauvais-Jarvis, Franck

doi:10.4161/isl.19747

Cited by 27 publications

(21 citation statements)

References 20 publications

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“…The dramatic differences in rapamycin-induced glucose intolerance and insulin resistance between the sexes in mice as noted here has previously been alluded to by Lamming et al (21) and Miller et al (28). While much has been done to better elucidate the role of E 2 and T in diabetes induced by various means in rats and mice (6,10,23,24,30,35,36,39,40), little has been done to explore their role in rapamycin-induced diabetes. We show here that E 2 plays a protective role against rapamycin-induced diabetes, with female mice becoming increasingly glucose-intolerant over a period of 10 wk postovariectomy and recovering glucose tolerance over 4 wk post-E 2 replacement.…”

Section: Discussionmentioning

confidence: 78%

“…Laboratory-based studies demonstrate that male mice are more prone to developing chemical-or high-fat dietinduced diabetes (30,36) and that diabetic symptoms improve after administration of E 2 (30). Female mice and rats have been shown to develop insulin resistance or glucose intolerance following exogenous T administration (23,30), ovariectomy (35,36), or knockout/inhibition of E 2 receptors such as ER␣ (24,35,39,40). In human-based studies, a decrease in E 2 levels in women, or polymorphisms in its receptor ER␣ in men have been associated with increased risk of diabetes onset (1,26).…”

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confidence: 98%

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Chronic rapamycin treatment causes diabetes in male mice

Schindler

Partap

Patchen

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Current evidence indicates that the mammalian target of rapamycin inhibitor rapamycin both increases longevity and, seemingly contradictorily, impairs glucose homeostasis. Most studies exploring the dimensions of this paradox have been based on rapamycin treatment in mice for up to 20 wk. We sought to better understand the metabolic effects of oral rapamycin over a substantially longer period of time in HET3 mice. We observed that treatment with rapamycin for 52 wk induced diabetes in male mice, characterized by hyperglycemia, significant urine glucose levels, and severe glucose and pyruvate intolerance. Glucose intolerance occurred in male mice by 4 wk on rapamycin and could be only partially reversed with cessation of rapamycin treatment. Female mice developed moderate glucose intolerance over 1 yr of rapamycin treatment, but not diabetes. The role of sex hormones in the differential development of diabetic symptoms in male and female mice was further explored. HET3 mice treated with rapamycin for 52 wk were gonadectomized and monitored over 10 wk. Castrated male mice remained glucose intolerant, while ovariectomized females developed significant glucose intolerance over the same time period. Subsequent replacement of 17β-estradiol (E2) in ovariectomized females promoted a recovery of glucose tolerance over a 4-wk period, suggesting the protective role of E2 against rapamycin-induced diabetes. These results indicate that 1) oral rapamycin treatment causes diabetes in male mice, 2) the diabetes is partially reversible with cessation of treatment, and 3) E2 plays a protective role against the development of rapamycin-induced diabetes.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 98%

Chronic rapamycin treatment causes diabetes in male mice

Schindler

Partap

Patchen

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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show abstract

“…Unlike tamoxifen, raloxifene did not increase triglyceride concentrations in HepG2 human hepatocarcinoma cells in the absence or presence of oleic acid [32]. However, raloxifene prevented triglyceride accumulation in rat INS-1 insulin-producing cells under lipogenic conditions [58]. Thus, the effect of raloxifene on preventing triglyceride accumulation seems to be tissue-specific.…”

Section: The Effects Of Raloxifene On Metabolismmentioning

confidence: 82%

Effect of selective estrogen receptor modulators on metabolic homeostasis

Lovre

Mauvais-Jarvis

2016

Biochimie

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“…ERα has been linked to glucose-stimulated insulin biosynthesis and the promotion of β-cell survival from apoptotic stimuli, while ERβ increases glucose-stimulated insulin secretion. In contrast, estrogen action via GPER protects β cells from apoptosis, resulting in glucose-stimulated insulin secretion and lipid homeostasis without affecting insulin biosynthesis [Tiano and Mauvais-Jarvis, 2012;Ropero et al, 2012]. Furthermore, GPER mediated growth factor activation may have important implications for homeostatic responses in the metabolic system.…”

Section: Energy Homeostasis Metabolic Effects and Bone Remodelingmentioning

confidence: 89%