Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance
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چکیده
منابع مشابه
PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance.
Inadequate compensatory beta cell hyperplasia in insulin-resistant states triggers the development of overt diabetes. The mechanisms that underlie this crucial adaptive response are not fully defined. Here we show that the compensatory islet-growth response to insulin resistance in 2 models--insulin receptor (IR)/IR substrate-1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) m...
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Transgenic nonobese diabetic mice were created in which insulin expression was targeted to proopiomelanocortin-expressing pituitary cells. Proopiomelanocortin-expressing intermediate lobe pituitary cells efficiently secrete fully processed, mature insulin via a regulated secretory pathway, similar to islet beta cells. However, in contrast to the insulin-producing islet beta cells, the insulin-p...
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insulin-resistance, β-cells compensate for this hormonal resistance for long periods of time by an increase in secretory capacity and in β-cell mass. In animal models of insulin-resistance there is islet hyperplasia (1–3) and very recently a clear correlation between BMI and β-cells mass was shown in humans (4). The driving forces that can contribute to the increased β-cell mass in insulin-resi...
متن کاملCyclin D2 Is Essential for the Compensatory β-Cell Hyperplastic Response to Insulin Resistance in Rodents
OBJECTIVE A major determinant of the progression from insulin resistance to the development of overt type 2 diabetes is a failure to mount an appropriate compensatory beta-cell hyperplastic response to maintain normoglycemia. We undertook the present study to directly explore the significance of the cell cycle protein cyclin D2 in the expansion of beta-cell mass in two different models of insul...
متن کاملIslet adaptation to insulin resistance: mechanisms and implications for intervention.
Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. The relation between insulin sensitivity and secretion is curvilinear and mathematically best described as a hyperbolic relation. Several potential mediators have been suggested to be signals for the beta cell...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2007
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.0608703104