scholarly journals Transcriptional Regulation of Glucose Sensors in Pancreatic β-Cells and Liver: An Update

Sensors ◽  
2010 ◽  
Vol 10 (5) ◽  
pp. 5031-5053 ◽  
Author(s):  
Jin-Sik Bae ◽  
Tae-Hyun Kim ◽  
Mi-Young Kim ◽  
Joo-Man Park ◽  
Yong-Ho Ahn
Keyword(s):  
Transcriptional Regulation ◽  
Glucose Sensors ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals The Krüppel-Like Protein Gli-Similar 3 (Glis3) Functions as a Key Regulator of Insulin Transcription

2013 ◽  
Vol 27 (10) ◽  
pp. 1692-1705 ◽  
Author(s):  
Gary T. ZeRuth ◽  
Yukimasa Takeda ◽  
Anton M. Jetten
Keyword(s):  
Transcriptional Regulation ◽  
Regulatory Region ◽  
Neonatal Diabetes ◽  
Creb Binding Protein ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Synergistic Activation ◽  
Transcriptional Regulatory ◽  
Insulin Promoter ◽  
Regulatory Complex

Transcriptional regulation of insulin in pancreatic β-cells is mediated primarily through enhancer elements located within the 5′ upstream regulatory region of the preproinsulin gene. Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription. In this report, we examined in detail the synergistic activation of insulin transcription by Glis3 with coregulators, CREB-binding protein (CBP)/p300, pancreatic and duodenal homeobox 1 (Pdx1), neuronal differentiation 1 (NeuroD1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). Our data show that Glis3 expression, the binding of Glis3 to GlisBS, and its recruitment of CBP are required for optimal activation of the insulin promoter in pancreatic β-cells not only by Glis3, but also by Pdx1, MafA, and NeuroD1. Mutations in the GlisBS or small interfering RNA−directed knockdown of GLIS3 diminished insulin promoter activation by Pdx1, NeuroD1, and MafA, and neither Pdx1 nor MafA was able to stably associate with the insulin promoter when the GlisBS were mutated. In addition, a GlisBS mutation in the INS promoter implicated in the development of neonatal diabetes similarly abated activation by Pdx1, NeuroD1, and MafA that could be reversed by increased expression of exogenous Glis3. We therefore propose that recruitment of CBP/p300 by Glis3 provides a scaffold for the formation of a larger transcriptional regulatory complex that stabilizes the binding of Pdx1, NeuroD1, and MafA complexes to their respective binding sites within the insulin promoter. Taken together, these results indicate that Glis3 plays a pivotal role in the transcriptional regulation of insulin and may serve as an important therapeutic target for the treatment of diabetes.

Transcriptional regulation of the IAPP gene in pancreatic β-cells

2004 ◽  
Vol 1681 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Louisa M.A. Shepherd ◽  
Susan C. Campbell ◽  
Wendy M. Macfarlane
Keyword(s):  
Transcriptional Regulation ◽  
Β Cells ◽  
Pancreatic Β Cells

MICROCHEMICAL ASSAYS OF GLUCOSE AND GLUCOSE-6-PHOSPHATE IN MAMMALIAN PANCREATIC β-CELLS

1968 ◽  
Vol 59 (3) ◽  
pp. 479-486 ◽  
Author(s):  
Lars-Ake Idahl ◽  
Bo Hellman
Keyword(s):  
Glucose Level ◽  
Exocrine Pancreas ◽  
The Other ◽  
Wide Concentration Range ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Enzymatic Cycling ◽  
Glucose Diffusion ◽  
Significant Barrier ◽  
The Brain

ABSTRACT The combination of enzymatic cycling and fluorometry was used for measuring glucose and glucose-6-phosphate in pancreatic β-cells from obese-hyperglycaemic mice. The glucose level of the β-cells corresponded to that of serum over a wide concentration range. In the exocrine pancreas, on the other hand, a significant barrier to glucose diffusion across the cell membranes was demonstrated. During 5 min of ischaemia, the glucose level remained practically unchanged in the β-cells while it increased in the liver and decreased in the brain. The observation that the pancreatic β-cells are characterized by a relatively low ratio of glucose-6-phosphate to glucose may be attributed to the presence of a specific glucose-6-phosphatase.

scholarly journals Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ionel Sandovici ◽  
Constanze M. Hammerle ◽  
Sam Virtue ◽  
Yurena Vivas-Garcia ◽  
Adriana Izquierdo-Lahuerta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Homeostasis ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Chow Diet ◽  
Genome Wide Association Studies ◽  
Cell Plasticity ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

AbstractWhen exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic β-cells (Igf2βKO) in mice. We show that autocrine actions of IGF2 are not critical for β-cell development, or for the early post-natal wave of β-cell remodelling. Additionally, adult Igf2βKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2βKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2βKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2βKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of β-cell IGF2 during early development determine their adaptive capacity in adult life.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

scholarly journals Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR‐29 family

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Jing Li ◽  
Yujing Zhang ◽  
Yangyang Ye ◽  
Dameng Li ◽  
Yuchen Liu ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Β Cells ◽  
Pancreatic Β Cells
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