scholarly journals Function and Gene Expression of Islets Experimentally Transplanted to Muscle and Omentum

2020 ◽  
Vol 29 ◽  
pp. 096368972096018
Author(s):  
Daniel Espes ◽  
Hanna Liljebäck ◽  
Petra Franzén ◽  
My Quach ◽  
Joey Lau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Beta Cell ◽  
Islet Transplantation ◽  
Glucose Transporter ◽  
Cell Function ◽  
Greater Omentum ◽  
Intravenous Glucose ◽  
Glucose Transporter 2 ◽  
Implantation Sites

Islet transplantation to the liver is a potential curative treatment for patients with type 1 diabetes. Muscle and the greater omentum are two alternative implantation sites, which can provide excellent engraftment and hold potential as future sites for stem-cell-derived beta-cell replacement. We evaluated the functional outcome after islet transplantation to muscle and omentum and found that alloxan-diabetic animals were cured with a low number of islets (200) at both sites. The cured animals had a normal area under the curve blood glucose response to intravenous glucose, albeit animals with intramuscular islet grafts had increased 120-min blood glucose levels. They also demonstrated an exaggerated counter regulatory response to hypoglycemia. The expression of genes important for beta-cell function was, at both implantation sites, comparable to that in native pancreatic islets. The gene expression of insulin (INS1 and INS2) and glucose transporter-2 was even increased, and the expression of lactate dehydrogenase decreased, at both sites when compared to native islets. We conclude that muscle and omentum provide excellent conditions for engraftment of transplanted islets. When compared to control, 200 islets implanted to the omentum displayed a restored glucose tolerance, whereas animals with intramuscular islet grafts of similar size displayed mild glucose intolerance.

scholarly journals Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2

2000 ◽  
Vol 164 (3) ◽  
pp. 277-286 ◽  
Author(s):  
A Petryk ◽  
D Fleenor ◽  
P Driscoll ◽  
M Freemark
Keyword(s):  
Gene Expression ◽  
Beta Cell ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Insulin Gene ◽  
Luciferase Reporter ◽  
Insulin Production ◽  
Glucose Transporter 2 ◽  
Insulin Gene Expression ◽  
Insulin Gene Transcription

Previous studies have shown that lactogenic hormones stimulate beta-cell proliferation and insulin production in pancreatic islets. However, all such studies have been conducted in cells incubated in medium containing glucose. Since glucose independently stimulates beta-cell replication and insulin production, it is unclear whether the effects of prolactin (PRL) on insulin gene expression are exerted directly or through the uptake and/or metabolism of glucose. We examined the interactions between glucose and PRL in the regulation of insulin gene transcription and the expression of glucose transporter-2 (glut-2) and glucokinase mRNAs in rat insulinoma (INS-1) cells. In the presence of 5.5 mM glucose, the levels of preproinsulin and glut-2 mRNAs in PRL-treated cells exceeded the levels in control cells (1.7-fold, P<0.05 and 2-fold, P<0.05 respectively). The maximal effects of PRL were noted at 24-48 h of incubation. PRL had no effect on the levels of glucokinase mRNA. The higher levels of glut-2 mRNA were accompanied by an increase in the number of cellular glucose transporters, as demonstrated by a 1. 4- to 2.4-fold increase in the uptake of 2-deoxy-d-[(3)H]glucose in PRL-treated INS-1 cells (P<0.001). These findings suggested that the insulinotropic effect of PRL is mediated, in part, by induction of glucose transport and/or glucose metabolism. Nevertheless, even in the absence of glucose, PRL stimulated increases in the levels of preproinsulin mRNA (3.4-fold higher than controls, P<0.0001) and glut-2 mRNA (2-fold higher than controls, P<0.01). These observations suggested that PRL exerts glucose-independent as well as glucose-dependent effects on insulin gene expression. Support for this hypothesis was provided by studies of insulin gene transcription using INS-1 cells transfected with a plasmid containing the rat insulin 1 promoter linked to a luciferase reporter gene. Glucose and PRL, alone and in combination, stimulated increases in cellular luciferase activity. The relative potencies of glucose (5.5 mM) alone, PRL alone, and glucose plus PRL in combination were 2.2 (P<0.001), 3.4 (P<0.01), and 7.9 (P<0.0001) respectively. Our findings suggest that glucose and PRL act synergistically to induce insulin gene transcription.

Glucose transporter 2 gene polymorphisms and beta-cell function in isolated human pancreatic islets

2009 ◽  
Vol 35 (2) ◽  
pp. 155-156 ◽  
Author(s):  
S. Del Guerra ◽  
R. Lupi ◽  
V. D’Aleo ◽  
F. Filipponi ◽  
U. Boggi ◽  
...  
Keyword(s):  
Beta Cell ◽  
Pancreatic Islets ◽  
Beta Cell Function ◽  
Gene Polymorphisms ◽  
Glucose Transporter ◽  
Cell Function ◽  
Human Pancreatic Islets ◽  
Glucose Transporter 2

CGM Shows Islet Transplantation Prevents Hypoglycemia, Correcting Time in Range and Reducing Glycemic Variability, Despite Subnormal Beta-Cell Function

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 143-OR ◽  
Author(s):  
SHAREEN FORBES ◽  
TOLU OLUTOYIN OLATEJU ◽  
ANNA LAM ◽  
JOHN CASEY ◽  
JOHN CAMPBELL ◽  
...  
Keyword(s):  
Beta Cell ◽  
Islet Transplantation ◽  
Beta Cell Function ◽  
Cell Function ◽  
Glycemic Variability ◽  
Time In Range

Efficacy and cardiovascular safety of Thiazolidinediones

2020 ◽  
Vol 15 ◽  
Author(s):  
Raveendran Arkiath Veettil ◽  
Cornelius James Fernandez ◽  
Koshy Jacob
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cardiovascular Safety ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

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 zinc transporter Zip14 (SLC39a14) affects Beta-cell Function: Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Trine Maxel ◽  
Kamille Smidt ◽  
Charlotte C. Petersen ◽  
Bent Honoré ◽  
Anne K. Christensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Zinc Transporter

scholarly journals A Systematic Review of Beta Cell Function in Adults of Black African Ethnicity

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
M. Ladwa ◽  
O. Hakim ◽  
S. A. Amiel ◽  
L. M. Goff
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Normal Glucose Tolerance ◽  
Qualitative Synthesis ◽  
Intravenous Glucose ◽  
Black African

Background. Understanding ethnic differences in beta cell function has important implications for preventative and therapeutic strategies in populations at high risk of type 2 diabetes (T2D). The existing literature, largely drawn from work in children and adolescents, suggests that beta cell function in black African (BA) populations is upregulated when compared to white Europeans (WE). Methods. A systematic literature search was undertaken in June 2018 to identify comparative studies of beta cell function between adults (>age 18 years) of indigenous/diasporic BA and WE ethnicity. All categories of glucose tolerance and all methodologies of assessing beta cell function in vivo were included. Results. 41 studies were identified for inclusion into a qualitative synthesis. The majority were studies in African American populations (n=30) with normal glucose tolerance (NGT)/nondiabetes (n=25), using intravenous glucose stimulation techniques (n=27). There were fewer studies in populations defined as only impaired fasting glucose/impaired glucose tolerance (IFG/IGT) (n=3) or only T2D (n=3). Although BA broadly exhibited greater peripheral insulin responses than WE, the relatively small number of studies which measured C-peptide to differentiate between beta cell insulin secretion and hepatic insulin extraction (n=14) had highly variable findings. In exclusively IGT or T2D cohorts, beta cell insulin secretion was found to be lower in BA compared to WE. Conclusions. There is inconsistent evidence for upregulated beta cell function in BA adults, and they may in fact exhibit greater deficits in insulin secretory function as glucose intolerance develops.

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