β-cell insulin receptor deficiency during in utero development induces an islet compensatory overgrowth response

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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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Growth hormone receptor deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice

Growth hormone (GH), acting through its receptor (GHR), is essential for somatic growth and development and maintaining metabolic homeostasis. GHR gene deficient (GHR) mice exhibit drastically diminished IGF-I levels, proportional growth retardation, elevated insulin sensitivity and reduced islet β-cell mass. Unlike the liver which is mostly unaffected by changes in the IGF-I level, skeletal mu...

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Growth hormone receptor gene deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice.

Growth hormone (GH), acting through its receptor (GHR), is essential for somatic growth and development and maintaining metabolic homeostasis. GHR gene-deficient (GHR(-/-)) mice exhibit drastically diminished insulin-like growth factor-I (IGF-I) levels, proportional growth retardation, elevated insulin sensitivity, and reduced islet beta-cell mass. Unlike the liver, which is mostly unaffected b...

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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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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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ژورنال

عنوان ژورنال: Oncotarget

سال: 2016

ISSN: 1949-2553

DOI: 10.18632/oncotarget.10342