PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance

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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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Reduced 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...

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Cyclin 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...

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β-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...

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The changes of serum insulin in response to resistance training with emphasis on FOXO1 in pancreas of diabetes rats

Introduction: Decreased insulin sensitivity and its secretion of pancreas increase the risk of developing type 2 diabetes (T2D). In the present study it was aimed to assess the effect of resistance training on Forkhead box protein O1 (FOXO1) expression in pancreas tissue, serum insulin, and insulin sensitivity in obese rats with T2D. Materials and Methods: T2D was induced by high fa...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2004

ISSN: 0021-9738

DOI: 10.1172/jci200421845