Iron overload in Hepc1(-/-) mice is not impairing glucose homeostasis.
Diabetes Mellitus is found with increasing frequency in iron overload patients with hemochromatosis. In these conditions, the pancreas shows predominant iron overload in acini but also islet beta-cells. We assess glucose homeostasis status in iron-overloaded hepcidin-deficient mice. These mice presented with heavy pancreatic iron deposits but only in the acini. The beta-cell function was found unaffected with a normal production and secretion of insulin. The mutant mice were not diabetic, responded as the control group to glucose and insulin challenges, with no alteration of insulin signalling in the muscle and the liver. These results indicate that, beta-cells iron deposits-induced decreased insulin secretory capacity might be of primary importance to trigger diabetes in hemochromatosic patients.
Ramey
G
G
Institut Cochin, Département Endocrinologie Métabolisme et Cancer, Paris, F-75014, France.
Faye
A
A
Durel
B
B
Viollet
B
B
Vaulont
S
S
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000172:deficiency* / Q000235:genetics; D003920:Diabetes Mellitus / Q000209:etiology; D005947:Glucose / Q000378:metabolism*; D006432:Hemochromatosis / Q000150:complications / Q000378:metabolism; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology; D019190:Iron Overload / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D007328:Insulin; D005947:Glucose