scholarly journals β-Cell-targeted Overexpression of Phosphodiesterase 3B in Mice Causes Impaired Insulin Secretion, Glucose Intolerance, and Deranged Islet Morphology

2004 ◽  
Vol 279 (15) ◽  
pp. 15214-15222 ◽  
Author(s):  
Linda Härndahl ◽  
Nils Wierup ◽  
Sven Enerbäck ◽  
Hindrik Mulder ◽  
Vincent C. Manganiello ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Intolerance ◽  
Β Cell ◽  
Impaired Insulin Secretion ◽  
Islet Morphology ◽  
Impaired Insulin ◽  
Phosphodiesterase 3B

scholarly journals β-Cell–Specific Deletion of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) Reductase Causes Overt Diabetes due to Reduction of β-Cell Mass and Impaired Insulin Secretion

Diabetes ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2352-2363
Author(s):  
Shoko Takei ◽  
Shuichi Nagashima ◽  
Akihito Takei ◽  
Daisuke Yamamuro ◽  
Tetsuji Wakabayashi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Coenzyme A ◽  
Cell Mass ◽  
Β Cell ◽  
Impaired Insulin Secretion ◽  
Overt Diabetes ◽  
Impaired Insulin ◽  
Specific Deletion ◽  
Coenzyme A Reductase

scholarly journals Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

2008 ◽  
Vol 105 (10) ◽  
pp. 3992-3997 ◽  
Author(s):  
N. Gustavsson ◽  
Y. Lao ◽  
A. Maximov ◽  
J.-C. Chuang ◽  
E. Kostromina ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Intolerance ◽  
Mutant Mice ◽  
Null Mutant ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin ◽  
Null Mutant Mice

Glucose Intolerance and Impaired Insulin Secretion by Prostaglandin A1in Fasting Anesthetized Dogs

Endocrinology ◽  
1973 ◽  
Vol 92 (1) ◽  
pp. 31-34 ◽  
Author(s):  
LUIGI SACCA ◽  
FRANCO RENGO ◽  
MASSIMO CHIARIELLO ◽  
MARIO CONDORELLI
Keyword(s):  
Insulin Secretion ◽  
Glucose Intolerance ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin ◽  
Anesthetized Dogs

scholarly journals Overexpression of FoxO1 in the Hypothalamus and Pancreas Causes Obesity and Glucose Intolerance

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 659-671 ◽  
Author(s):  
Hye-Jin Kim ◽  
Masaki Kobayashi ◽  
Tsutomu Sasaki ◽  
Osamu Kikuchi ◽  
Kosuke Amano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Secretion ◽  
Glucose Intolerance ◽  
Insulin Signaling ◽  
Uncoupling Protein ◽  
Cell Mass ◽  
Peroxisome Proliferator ◽  
Β Cells ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

Recent studies have revealed that insulin signaling in pancreatic β-cells and the hypothalamus is critical for maintaining nutrient and energy homeostasis, the failure of which are hallmarks of metabolic syndrome. We previously reported that forkhead transcription factor forkhead box-containing protein of the O subfamily (FoxO)1, a downstream effector of insulin signaling, plays important roles in β-cells and the hypothalamus when we investigated the roles of FoxO1 independently in the pancreas and hypothalamus. However, because metabolic syndrome is caused by the combined disorders in hypothalamus and pancreas, to elucidate the combined implications of FoxO1 in these organs, we generated constitutively active FoxO1 knockin (KI) mice with specific activation in both the hypothalamus and pancreas. The KI mice developed obesity, insulin resistance, glucose intolerance, and hypertriglyceridemia due to increased food intake, decreased energy expenditure, and impaired insulin secretion, which characterize metabolic syndrome. The KI mice also had increased hypothalamic Agouti-related protein and neuropeptide Y levels and decreased uncoupling protein 1 and peroxisome proliferator-activated receptor γ coactivator 1α levels in adipose tissue and skeletal muscle. Impaired insulin secretion was associated with decreased expression of pancreatic and duodenum homeobox 1 (Pdx1), muscyloaponeurotic fibrosarcoma oncogene homolog A (MafA), and neurogenic differentiation 1 (NeuroD) in islets, although β-cell mass was paradoxically increased in KI mice. Based on these results, we propose that uncontrolled FoxO1 activation in the hypothalamus and pancreas accounts for the development of obesity and glucose intolerance, hallmarks of metabolic syndrome.

scholarly journals c-Myc directly induces both impaired insulin secretion and loss of β-cell mass, independently of hyperglycemia in vivo

Islets ◽  
2010 ◽  
Vol 2 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Linda Cheung ◽  
Sevasti Zervou ◽  
Göran Mattsson ◽  
Sylvie Abouna ◽  
Luxian Zhou ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Mass ◽  
Β Cell ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

scholarly journals Glucose Intolerance and Impaired Insulin Secretion in Pancreas-Specific Signal Transducer and Activator of Transcription-3 Knockout Mice Are Associated with Microvascular Alterations in the Pancreas

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2050-2059 ◽  
Author(s):  
Elena Kostromina ◽  
Natalia Gustavsson ◽  
Xiaorui Wang ◽  
Chun-Yan Lim ◽  
George K. Radda ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Intolerance ◽  
Endocrine Pancreas ◽  
Isolated Islets ◽  
Signal Transducer ◽  
Microvascular Network ◽  
Impaired Insulin Secretion ◽  
Stat3 Signaling ◽  
Impaired Insulin

Maintenance of glucose homeostasis depends on adequate amount and precise pattern of insulin secretion, which is determined by both β-cell secretory processes and well-developed microvascular network within endocrine pancreas. The development of highly organized microvasculature and high degrees of capillary fenestrations in endocrine pancreas is greatly dependent on vascular endothelial growth factor-A (VEGF-A) from islet cells. However, it is unclear how VEGF-A production is regulated in endocrine pancreas. To understand whether signal transducer and activator of transcription (STAT)-3 is involved in VEGF-A regulation and subsequent islet and microvascular network development, we generated a mouse line carrying pancreas-specific deletion of STAT3 (p-KO) and performed physiological analyses both in vivo and using isolated islets, including glucose and insulin tolerance tests, and insulin secretion measurements. We also studied microvascular network and islet development by using immunohistochemical methods. The p-KO mice exhibited glucose intolerance and impaired insulin secretion in vivo but normal insulin secretion in isolated islets. Microvascular density in the pancreas was reduced in p-KO mice, along with decreased expression of VEGF-A, but not other vasotropic factors in islets in the absence of pancreatic STAT3 signaling. Together, our study suggests that pancreatic STAT3 signaling is required for the normal development and maintenance of endocrine pancreas and islet microvascular network, possibly through its regulation of VEGF-A.

scholarly journals Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

2015 ◽  
Vol 93 (5) ◽  
pp. 511-521 ◽  
Author(s):  
Tasnim Dayeh ◽  
Charlotte Ling
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Impaired Insulin Secretion ◽  
Expression Of Genes ◽  
Impaired Insulin

β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes.

Impaired insulin secretion and β-cell loss in tissue-specific knockout mice with mitochondrial diabetes

10.1038/81649 ◽  
2000 ◽  
Vol 26 (3) ◽  
pp. 336-340 ◽  
Author(s):  
José P. Silva ◽  
Martin Köhler ◽  
Caroline Graff ◽  
Anders Oldfors ◽  
Mark A. Magnuson ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Knockout Mice ◽  
Cell Loss ◽  
Β Cell ◽  
Tissue Specific ◽  
Impaired Insulin Secretion ◽  
Mitochondrial Diabetes ◽  
Impaired Insulin
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