scholarly journals Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood

2002 ◽  
pp. 129-141 ◽  
Author(s):  
H Hui ◽  
R Perfetti
Keyword(s):  
Islet Cell ◽  
Glucose Transporter ◽  
Cell Function ◽  
Islet Cells ◽  
Cell Physiology ◽  
Islet Amyloid ◽  
Dominant Form ◽  
Insulin Promoter ◽  
Dual Action ◽  
Islet Cell Function

Pancreas duodenum homeobox-1 (PDX-1) (also known as insulin promoter factor-1, islet/duodenum homeobox-1, somatostatin transactivating factor-1, insulin upstream factor-1 and glucose-sensitive factor) is a transcription factor encoded by a Hox-like homeodomain gene. In humans and other animal species, the embryonic development of the pancreas requires PDX-1, as demonstrated by the identification of an individual with pancreatic agenesis resulting from a mutation that impaired the transcription of a functionally active PDX-1 protein. In adult subjects, PDX-1 is essential for normal pancreatic islet function as suggested by its regulatory action on the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, the glucose transporter type 2 and glucokinase. Furthermore, heterozygous mutations of PDX-1 have been linked to a type of autosomal dominant form of diabetes mellitus known as maturity onset diabetes of the young type 4. The dual action of PDX-1, as a differentiation factor during embryogenesis and as a regulator of islet cell physiology in mature islet cells, underscores the unique role of PDX-1 in health and disease of the human endocrine pancreas.

Effect of Glucose Metabolism-Associated Protein-1 on Exendin-4-Treated Pancreatic Islet Cell Function

2020 ◽  
Vol 10 (7) ◽  
pp. 1015-1021
Author(s):  
Jing Feng ◽  
Cuiwen Kong ◽  
Min Wang ◽  
Yingchuan Xu ◽  
Yingwei Chang
Keyword(s):  
Cell Proliferation ◽  
Glucose Metabolism ◽  
Islet Cell ◽  
Caspase 3 ◽  
Cell Function ◽  
Islet Cells ◽  
Control Group ◽  
Sod Activity ◽  
Fas L ◽  
Islet Cell Function

Exendin-4 regulates blood sugar. Glucose metabolism-associated protein-1 (GMRP-1) regulates islet cell function. Therefore, this paper intends to analyze the effect of GMRP-1 on Exendin-4treated islet cells. The islet cell MIN6 cells were separated into control group, Exendin-4 group, GMRP-1 overexpressing+ Exendin-4 group, and GMRP-1 siRNA+ Exendin-4 group followed by analysis of the expression of GMRP-1 by quantitative real-time PCR and Western blot, cell proliferation by MTT, cell apoptosis by flow cytometry, Bcl-2, Bax, Fas and Fas-L expression by real-time PCR, as well as caspase-3 activity, reactive oxygen species (ROS) and superoxide dismutase (SOD) activity. Exendin-4 and GMRP-1 overexpression+ Exendin-4 significantly increased GMRP-1 expression and promoted cell proliferation, decreased apoptotic rate and Caspase-3 activity, increased Bcl-2 and Fas-L expression, reduced Fas and Bax expression, as well as decreased ROS generation and increased SOD activity (P < 0 05), and the changes in GMRP-1 overexpression+ Exendin-4 group was more significant (P < 0 01). However, GMRP-1 siRNA+ Exendin-4 group significantly down-regulated GMRP-1 expression, decreased MIN6 cell prolifer- ation, increased cell apoptosis and Caspase-3 activity, decreased Bcl-2 and Fas-L expression, elevated Fas and Bax expression, increased ROS content and decreased SOD activity compared to control group and Exendin-4 group (P < 0 05). Up-regulation of GMRP-1 expression promoted Exendin-4-induced proliferation and inhibited apoptosis of islet cells. Down-regulation of GMRP-1 expression reversed Exendin-4's effect on islet cells.

1774-P: Neurally Mediated Prandial Islet-Cell Function Is Glucose-Independent and Preserved after Gastric Bypass and Sleeve Gastrectomy

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1774-P
Author(s):  
HENRI HONKA ◽  
ANAS M. AL ZUBAIDI ◽  
RALPH A. DEFRONZO ◽  
AMALIA GASTALDELLI ◽  
MARZIEH SALEHI
Keyword(s):  
Gastric Bypass ◽  
Sleeve Gastrectomy ◽  
Islet Cell ◽  
Cell Function ◽  
Islet Cell Function

Effects of l-leucine, its 2-keto acid metabolite and its nonmetabolized analogue on rat tumoral islet cell function

1988 ◽  
Vol 1 (1) ◽  
pp. 69-76 ◽  
Author(s):  
V. Leclercq-Meyer ◽  
J. Marchand ◽  
A. Sener ◽  
F. Blachier ◽  
W. J. Malaisse
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Islet Cells ◽  
Adenine Nucleotides ◽  
Secretory Response ◽  
Acid Metabolite ◽  
Dual Effect ◽  
Islet Cell Function ◽  
Insulinoma Cells ◽  
Stimulation Of

ABSTRACT l-Leucine and 2-ketoisocaproate stimulated insulin release from perifused rat tumoral islet cells (RINm5F line). The secretory response coincided with an increase in the intracellular ATP/ADP ratio, a stimulation of 45Ca outflow from cells perifused in the presence of extracellular Ca2+, and an increase in 32P efflux from cells prelabelled with radioactive orthophosphate. In contrast to d-glucose, however, l-leucine or 2-ketoisocaproate failed to decrease 86Rb outflow, to inhibit 45Ca outflow from cells perifused in the absence of Ca2+ and to enhance the labelling of inositol-containing phospholipids in cells exposed to myo-[2-3H]inositol. These findings suggest that d-glucose, l-leucine and 2-ketoisocaproate exert dissimilar effects on the subcellular distribution of adenine nucleotides and/or 86Rb. The nonmetabolized analogue of l-leucine, 2-aminobicyclo-[2.2.1]heptane-2-carboxylic acid (BCH), also caused an initial stimulation of insulin release and 32P efflux, but this was soon followed by a severe and irreversible inhibition of insulin output, associated with a permanent enhancement of 86Rb outflow. The dual ionic and secretory response to BCH is interpreted in the light of its dual effect on the catabolism of endogenous amino and fatty acids, and raises the view that BCH could be used to interfere with the function of insulinoma cells.

SBP-101 Produces Atrophy of the Exocrine Pancreas and Exocrine Pancreatic Insufficiency while Preserving Islet Cell Function in Dogs

2017 ◽  
Vol 152 (5) ◽  
pp. S901
Author(s):  
Michael Walker ◽  
Suzanne Gagnon ◽  
Andy Kiorpes ◽  
Michael Cullen ◽  
Jan Wiegand ◽  
...  
Keyword(s):  
Exocrine Pancreas ◽  
Islet Cell ◽  
Cell Function ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency ◽  
Islet Cell Function

Effects of glucose and d-3-hydroxybutyrate on human pancreatic islet cell function

1985 ◽  
Vol 68 (5) ◽  
pp. 567-572 ◽  
Author(s):  
C. J. Rhodes ◽  
I. L. Campbell ◽  
T. M. Szopa ◽  
T. J. Biden ◽  
P. D. Reynolds ◽  
...  
Keyword(s):  
Insulin Release ◽  
Human Tissue ◽  
Islet Cell ◽  
Cell Function ◽  
Human Islets ◽  
Β Cell ◽  
Pancreatic Islet Cell ◽  
Sigmoidal Curve ◽  
Β Cell Function ◽  
Islet Cell Function

1. β-Cell function in human islets derived from a number of kidney donors was investigated by using various types of islet preparations. 2. With fresh islets, both insulin release and biosynthesis were increased by raising glucose concentrations, although the response was a variable one. 3. In fresh islets, the effects of 5 mmol of glucose/l on release were potentiated by 10 mmol of d-3-hydroxybutyrate/l. 4. Insulin release at 20 mmol of glucose/l was inhibited by adrenaline (0.1 mmol/l), and potentiated by theophylline (10 mmol/l) in the presence of 5 mmol of glucose/l, in islets cultured for 4 days. 5. After culture for 8 days, islets still showed an increase in insulin release and biosynthesis in response to glucose. 6. Pancreas slices derived from fresh human tissue also responded to increasing concentrations of glucose with a sigmoidal curve for insulin release.

Effects of pefloxacin on rat pancreatic islet cell function after 24-hour cold preservation

1997 ◽  
Vol 29 (4) ◽  
pp. 1984-1985
Author(s):  
P. Kwiatkowski ◽  
J. Puc ◽  
M. Rotbart-Fiedor ◽  
S.F. Oluwole ◽  
W. Rowinski ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Islet Cell ◽  
Cell Function ◽  
Pancreatic Islet Cell ◽  
Cold Preservation ◽  
Islet Cell Function ◽  
Rat Pancreatic Islet

Persistent expression of HNF6 in islet endocrine cells causes disrupted islet architecture and loss of beta cell function

Development ◽  
2000 ◽  
Vol 127 (13) ◽  
pp. 2883-2895 ◽  
Author(s):  
M. Gannon ◽  
M.K. Ray ◽  
K. Van Zee ◽  
F. Rausa ◽  
R.H. Costa ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Endocrine Cells ◽  
Spatial Organization ◽  
Glucose Transporter ◽  
Cell Function ◽  
Regulatory Element ◽  
Cell Physiology ◽  
Pancreatic Ducts ◽  
And Function

We used transgenesis to explore the requirement for downregulation of hepatocyte nuclear factor 6 (HNF6) expression in the assembly, differentiation, and function of pancreatic islets. In vivo, HNF6 expression becomes downregulated in pancreatic endocrine cells at 18. 5 days post coitum (d.p.c.), when definitive islets first begin to organize. We used an islet-specific regulatory element (pdx1(PB)) from pancreatic/duodenal homeobox (pdx1) gene to maintain HNF6 expression in endocrine cells beyond 18.5 d.p.c. Transgenic animals were diabetic. HNF6-overexpressing islets were hyperplastic and remained very close to the pancreatic ducts. Strikingly, alpha, delta, and PP cells were increased in number and abnormally intermingled with islet beta cells. Although several mature beta cell markers were expressed in beta cells of transgenic islets, the glucose transporter GLUT2 was absent or severely reduced. As glucose uptake/metabolism is essential for insulin secretion, decreased GLUT2 may contribute to the etiology of diabetes in pdx1(PB)-HNF6 transgenics. Concordantly, blood insulin was not raised by glucose challenge, suggesting profound beta cell dysfunction. Thus, we have shown that HNF6 downregulation during islet ontogeny is critical to normal pancreas formation and function: continued expression impairs the clustering of endocrine cells and their separation from the ductal epithelium, disrupts the spatial organization of endocrine cell types within the islet, and severely compromises beta cell physiology, leading to overt diabetes.

scholarly journals The Pathogenesis of Diabetes Mellitus

1970 ◽  
Vol 15 (9) ◽  
pp. 339-349 ◽  
Author(s):  
B. F. Clarke
Keyword(s):  
Diabetes Mellitus ◽  
Islet Cell ◽  
Genetic Factors ◽  
Cell Function ◽  
Single Individual ◽  
Additive Effects ◽  
Genetic Element ◽  
Close Relatives ◽  
Islet Cell Function ◽  
Overt Disease

The precise aetiology of diabetes mellitus remains unknown. There is clearly both a genetic element which is almost certainly multifactorial, due to the multiple and additive effects of genes especially in younger patients, together with environmental factors, especially in older patients. Evidence is increasing that the genetic element is associated with an underlying defect of the beta cells with a characteristic delayed and subnormal insulin secretion in response to glucose or other insulinogenic stimuli. The same hyposecretory response can often be found in many close relatives and in ‘prediabetes’ where standard carbohydrate tolerance is still normal. The nature of the defect of the beta cell, its link with the genetic mechanism, and the mechanism leading to total islet failure in some diabetics is not known. Many factors may be involved simultaneously in a single individual and apart from multiple genes, certain non-genetic factors such as obesity, pregnancy, infection and other stress which result in increased insulin antagonism, lead to additive strains on islet cell function, and may determine the onset of the overt disease in hereditarily predisposed individuals.

Deterioration of Islet  -Cell Function After Hemipancreatectomy in Dogs

Diabetes ◽  
1991 ◽  
Vol 40 (11) ◽  
pp. 1472-1479 ◽  
Author(s):  
J. I. Stagner ◽  
E. Samols
Keyword(s):  
Islet Cell ◽  
Cell Function ◽  
Islet Cell Function

scholarly journals IgGs from patients with amyotrophic lateral sclerosis and diabetes target CaVα2δ1 subunits impairing islet cell function and survival

2019 ◽  
Vol 116 (52) ◽  
pp. 26816-26822
Author(s):  
Yue Shi ◽  
Kyoung Sun Park ◽  
Seung Hyun Kim ◽  
Jia Yu ◽  
Kaixuan Zhao ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cell Function ◽  
Islet Cells ◽  
Causal Link ◽  
Mouse Islet ◽  
Voltage Dependent ◽  
Islet Cell Function ◽  
Als Patients ◽  
Lateral Sclerosis

Patients with amyotrophic lateral sclerosis (ALS) often show hallmarks of type 2 diabetes mellitus (T2DM). However, the causal link between ALS and T2DM has remained a mystery. We now demonstrate that 60% of ALS patients with T2DM (ALS-T2DM) have sera that exaggerated K+-induced increases in cytosolic free Ca2+concentration ([Ca2+]i) in mouse islet cells. The effect was attributed to the presence of pathogenic immunoglobulin Gs (IgGs) in ALS-T2DM sera. The pathogenic IgGs immunocaptured the voltage-dependent Ca2+(CaV) channel subunit CaVα2δ1 in the plasma membrane enhancing CaV1 channel-mediated Ca2+influx and [Ca2+]i, resulting in impaired mitochondrial function. Consequently, impairments in [Ca2+]idynamics, insulin secretion, and cell viability occurred. These data reveal that patients with ALS-T2DM carry cytotoxic ALS-T2DM-IgG autoantibodies that serve as a causal link between ALS and T2DM by immunoattacking CaVα2δ1 subunits. Our findings may lay the foundation for a pharmacological treatment strategy for patients suffering from a combination of these diseases.

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