Progesterone receptor knockout mice have an improved glucose homeostasis secondary to beta -cell proliferation.
Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female dbdb mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and dbdb mice. Furthermore, female, but not male, PR-- mice had lower fasting glycemia than PR++ mice and showed higher insulin levels on glucose injection. Pancreatic islets from female PR-- mice were larger and secreted more insulin consequent to an increase in beta-cell mass due to an increase in beta-cell proliferation. These findings demonstrate an important role of progesterone signaling in insulin release and pancreatic function and suggest that it affects the susceptibility to diabetes.
Picard
Frédéric
F
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche ScientifiqueInstitut National de la Santé et de la Recherche MédicalUniversité Louis Pasteur, 67404 Illkirch, France.
Wanatabe
Mitsuhiro
M
Schoonjans
Kristina
K
Lydon
John
J
O'Malley
Bert W
BW
Auwerx
Johan
J
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002452:Cell Count; D002455:Cell Division; D048429:Cell Size; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D016640:Diabetes, Gestational; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006727:Hormone Antagonists / Q000494:pharmacology; D006943:Hyperglycemia / Q000235:genetics; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015735:Mifepristone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000502:physiology*; D012727:Sex Characteristics; D015398:Signal Transduction
D001786:Blood Glucose; D006727:Hormone Antagonists; D007328:Insulin; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone; D005947:Glucose