Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics
نویسندگان
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...
متن کاملβ-cell insulin receptor deficiency during in utero development induces an islet compensatory overgrowth response
The presence of insulin receptor (IR) on β-cells suggests that insulin has an autocrine/paracrine role in the regulation of β-cell function. It has previously been reported that the β-cell specific loss of IR (βIRKO) leads to the development of impaired glycemic regulation and β-cell death in mice. However, temporally controlled βIRKO induced during the distinct transitions of fetal pancreas de...
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 کاملReduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis.
In type 2 diabetes mellitus, insulin resistance and an inadequate pancreatic beta-cell response to the demands of insulin resistance lead to impaired insulin secretion and hyperglycemia. Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. To investigate the role of PDX-1 in isl...
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: Journal of Proteome Research
سال: 2015
ISSN: 1535-3893,1535-3907
DOI: 10.1021/acs.jproteome.5b00587