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• W2091244663 abstract "The presented hypothesis identifies milk consumption as an environmental risk factor of Western diet promoting type 2 diabetes (T2D). Milk, commonly regarded as a valuable nutrient, exerts important endocrine functions as an insulinotropic, anabolic and mitogenic signalling system supporting neonatal growth and development. The presented hypothesis substantiates milk's physiological role as a signalling system for pancreatic β-cell proliferation by milk's ability to increase prolactin-, growth hormone and incretin-signalling. The proposed mechanism of milk-induced postnatal β-cell mass expansion mimics the adaptive prolactin-dependent proliferative changes observed in pregnancy. Milk signalling down-regulates the key transcription factor FoxO1 leading to up-regulation of insulin promoter factor-1 which stimulates β-cell proliferation, insulin secretion as well as coexpression of islet amyloid polypeptide (IAPP). The recent finding that adult rodent β-cells only proliferate by self-duplication is of crucial importance, because permanent milk consumption beyond the weaning period may continuously over-stimulate β-cell replication thereby accelerating the onset of replicative β-cell senescence. The long-term use of milk may thus increase endoplasmic reticulum (ER) stress and toxic IAPP oligomer formation by overloading the ER with cytotoxic IAPPs thereby promoting β-cell apoptosis. Both increased β-cell proliferation and β-cell apoptosis are hallmarks of T2D. This hypothesis gets support from clinical states of hyperprolactinaemia and progeria syndromes with early onset of cell senescence which are both associated with an increased incidence of T2D and share common features of milk signalling. Furthermore, the presented milk hypothesis of T2D is compatible with the concept of high ER stress in T2D and the toxic oligomer hypothesis of T2D and may explain the high association of T2D and Alzheimer disease." @default.
• W2091244663 created "2016-06-24" @default.
• W2091244663 creator A5014420805 @default.
• W2091244663 date "2011-04-01" @default.
• W2091244663 modified "2023-09-25" @default.
• W2091244663 title "Milk signalling in the pathogenesis of type 2 diabetes" @default.
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• W2091244663 doi "https://doi.org/10.1016/j.mehy.2010.12.017" @default.
• W2091244663 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21251764" @default.
• W2091244663 hasPublicationYear "2011" @default.
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