title: High fat programming of beta cell compensation, exhaustion, death and dysfunction.
abstract: Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease.
authors: Diabetes Discovery Platform, Medical Research Council, Tygerberg, Cape Town, South Africa.
authors: Marlon E
authors: ME
authors: Cerf
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002657:Child Development; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D007774:Lactation; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000503:physiopathology; D011236:Prediabetic State / Q000196:embryology / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology
chemical_list: D007328:Insulin
keywords: diabetes; hyperglycemia; insulin resistance; nutrition; obesity