scholarly journals MicroRNA‐29 expression in pancreatic islets correlates with the impairment of maternal glucose homeostasis induced by glucocorticoid excess in late pregnancy

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Patricia Rodrigues Lourenço Gomes ◽  
Maria Fernanda Rodrigues Graciano ◽  
Lucas Carminati Pantaleão ◽  
Camilo Lellis‐Santos ◽  
Angelo Rafael Carpinelli ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
Late Pregnancy ◽  
Maternal Glucose

scholarly journals Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ashley M. Fields ◽  
Kevin Welle ◽  
Elaine S. Ho ◽  
Clementina Mesaros ◽  
Martha Susiarjo
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Intolerance ◽  
Vitamin B6 ◽  
Serotonin Receptor ◽  
Dependent Manner ◽  
Β Cell ◽  
Vitamin B6 Deficiency ◽  
Maternal Glucose

AbstractIn pancreatic islets, catabolism of tryptophan into serotonin and serotonin receptor 2B (HTR2B) activation is crucial for β-cell proliferation and maternal glucose regulation during pregnancy. Factors that reduce serotonin synthesis and perturb HTR2B signaling are associated with decreased β-cell number, impaired insulin secretion, and gestational glucose intolerance in mice. Albeit the tryptophan-serotonin pathway is dependent on vitamin B6 bioavailability, how vitamin B6 deficiency impacts β-cell proliferation during pregnancy has not been investigated. In this study, we created a vitamin B6 deficient mouse model and investigated how gestational deficiency influences maternal glucose tolerance. Our studies show that gestational vitamin B6 deficiency decreases serotonin levels in maternal pancreatic islets and reduces β-cell proliferation in an HTR2B-dependent manner. These changes were associated with glucose intolerance and insulin resistance, however insulin secretion remained intact. Our findings suggest that vitamin B6 deficiency-induced gestational glucose intolerance involves additional mechanisms that are complex and insulin independent.

Effects of photobiomodulation on glucose homeostasis and morphometric parameters in pancreatic islets of diabetic mice

2021 ◽  
Author(s):  
Mirian Bonifacio ◽  
Izabelle Dias Benfato ◽  
Matheus de Almeida Cruz ◽  
Daniele Correia de Sales ◽  
Isabella Liba Pandolfo ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
Morphometric Parameters ◽  
Diabetic Mice

scholarly journals Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP)

2020 ◽  
Vol 8 (1) ◽  
pp. e000942
Author(s):  
Mouna El-Mehdi ◽  
Saloua Takhlidjt ◽  
Fayrouz Khiar ◽  
Gaëtan Prévost ◽  
Jean-Luc do Rego ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
Gene Knockout ◽  
Hepatic Glucose Production ◽  
Biologically Active ◽  
Mutant Mice ◽  
Insulin Production ◽  
Coding Region ◽  
The Impact

Introduction26RFa (pyroglutamyl RFamide peptide (QRFP)) is a biologically active peptide that has been found to control feeding behavior by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism.Research design and methods26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro26RFa was replaced by the iCre sequence. Energy and glucose metabolism was evaluated through measurement of complementary parameters. Morphological and physiological alterations of the pancreatic islets were also investigated.ResultsOur data do not reveal significant alteration of energy metabolism in the 26RFa-deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa mutant mice exhibited an altered glycemic phenotype with an increased hyperglycemia after a glucose challenge associated with an impaired insulin production, and an elevated hepatic glucose production. Two-dimensional and three-dimensional immunohistochemical experiments indicate that the insulin content of pancreatic β cells is much lower in the 26RFa−/− mice as compared with the wild-type littermates.ConclusionDisruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis, with in particular a deficit in insulin production by the pancreatic islets. These findings further support the notion that 26RFa is an important regulator of glucose homeostasis.

scholarly journals Glucose partitioning in the pregnant ewe: Effects of undernutrition and exercise

1990 ◽  
Vol 64 (2) ◽  
pp. 449-462 ◽  
Author(s):  
B. J. Leury ◽  
A. R. Bird ◽  
K. D. Chandler ◽  
A. W. Bell
Keyword(s):  
Glucose Uptake ◽  
Energy Requirement ◽  
Live Weight ◽  
Late Pregnancy ◽  
Maternal Blood ◽  
Whole Body ◽  
Entry Rate ◽  
Glucose Transfer ◽  
Glucose Supply ◽  
Maternal Glucose

Maternal whole-body glucose entry rate and uterine and umbilical net uptakes of glucose and oxygen were measured in single-pregnant ewes which were either well-fed throughout, or fed at 0.3–0.4 predicted energy requirement for 7–21 d during late pregnancy. All ewes were studied while standing at rest and then while walking on a treadmill at 0.7 m/s on a 10° slope for 60 min. Underfed ewes suffered significant decreases in live weight and had lower fetal, but not placental, weights at 140–144 d gestation. Undernutrition also caused large decreases in maternal glycaemia and glucose entry rate, which were associated with equally large decreases in uterine and umbilical net uptakes and O2 quotients of glucose, and with a decrease in placental glucose transfer capacity. Exercise caused increases in maternal blood concentration, entry rate and uterine net uptake of glucose, the magnitudes of which were not significantly affected by plane of nutrition. Umbilical glucose uptake and placental glucose transfer capacity increased during exercise in underfed but not fed ewes. The fractional distribution of maternal glucose to the pregnant uterus, and of uterine glucose uptake to the fetus, were unaltered by undernutrition; during exercise, a disproportionately small fraction of the increased maternal glucose supply went to the uterus. The results confirm that the ovine conceptus responds to nutritional reduction in maternal glucose availability in a manner similar to non-uterine maternal tissues. Major reductions in glucose supply appear to override putative glucose-sparing mechanisms which may operate to favour the conceptus in better-nourished animals.

scholarly journals MiR-206 is expressed in pancreatic islets and regulates glucokinase activity

2016 ◽  
Vol 311 (1) ◽  
pp. E175-E185 ◽  
Author(s):  
Manjula Vinod ◽  
Jay V. Patankar ◽  
Vinay Sachdev ◽  
Saša Frank ◽  
Wolfgang F. Graier ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
Posttranscriptional Regulation ◽  
Germ Line ◽  
In Silico Analysis ◽  
Liver Glycogen ◽  
Whole Body ◽  
The Metabolic Syndrome

Glucose homeostasis is a complex indispensable process, and its dysregulation causes hyperglycemia and type 2 diabetes mellitus. Glucokinase (GK) takes a central role in these pathways and is thus rate limiting for glucose-stimulated insulin secretion (GSIS) from pancreatic islets. Several reports have described the transcriptional regulation of Gck mRNA, whereas its posttranscriptional mechanisms of regulation, especially those involving microRNAs (miR), are poorly understood. In this study, we investigated the role of miR-206 as a posttranscriptional regulator of Gck. In addition, we examined the effects of miR-206 on glucose tolerance, GSIS, and gene expression in control and germ line miR-206 knockout (KO) mice fed either with chow or high-fat diet (HFD). MiR-206 was found in Gck-expressing tissues and was differentially altered in response to HFD feeding. Pancreatic islets showed the most profound induction in the expression of miR-206 in response to HFD. Chow- and HFD-fed miR-206KO mice have improved glucose tolerance and GSIS but unaltered insulin sensitivity. In silico analysis of Gck mRNA revealed a conserved 8-mer miR-206 binding site. Hence, the predicted regulation of Gck by miR-206 was confirmed in reporter and GK activity assays. Concomitant with increased GK activity, miR-206KO mice had elevated liver glycogen content and plasma lactate concentrations. Our findings revealed a novel mechanism of posttranscriptional regulation of Gck by miR-206 and underline the crucial role of pancreatic islet miR-206 in the regulation of whole body glucose homeostasis in a murine model that mimics the metabolic syndrome.

scholarly journals The long non-coding RNA Pax6os1/PAX6-AS1 modulates pancreatic β-cell identity and function

2020 ◽  
Author(s):  
Livia Lopez-Noriega ◽  
Rebecca Callingham ◽  
Aida Martinez-Sánchez ◽  
Grazia Pizza ◽  
Nejc Haberman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
High Glucose ◽  
High Fat Diet ◽  
High Fat ◽  
Β Cell ◽  
And Function

AbstractLong non-coding RNAs (lncRNAs) are emerging as crucial regulators of β-cell development and function. Consequently, the mis-expression of members of this group may contribute to the risk of type 2 diabetes (T2D). Here, we investigate roles for an antisense lncRNA expressed from the Pax6 locus (annotated as Pax6os1 in mice and PAX6-AS1 in humans) in β-cell function. The transcription factor Pax6 is required for the development of pancreatic islets and maintenance of a fully differentiated β-cell phenotype. Pax6os1/PAX6-AS1 expression was increased in pancreatic islets and β-cell lines at high glucose concentrations, in islets from mice fed a high fat diet, and in those from patients with type 2 diabetes. Silencing or deletion of Pax6os1/PAX6-AS1 in MIN6 cells and EndoC-βH1cells, respectively, upregulated β-cell signature genes, including insulin. Moreover, shRNA-mediated silencing of PAX6-AS1 in human islets not only increased insulin mRNA, but also enhanced glucose-stimulated insulin secretion and calcium dynamics. In contrast, inactivation of Pax6os1 in mice was largely without effect on glucose homeostasis, though female Pax6os1 null mice on high fat diet (HFD) showed a tendency towards enhanced glucose clearance. Together, our results suggest that increased expression of PAX6-AS1 at high glucose levels may contribute to β-cell dedifferentiation and failure in some forms of type 2 diabetes. Thus, targeting PAX6-AS1 may provide a promising strategy to enhance insulin secretion and improve glucose homeostasis in type 2 diabetes.

scholarly journals Glucose homeostasis is impaired in mice deficient for the neuropeptide 26RFa (QRFP)

2019 ◽  
Author(s):  
Mouna El Mehdi ◽  
Saloua Takhlidjt ◽  
Fayrouz Khiar ◽  
Gaëtan Prévost ◽  
Jean-Luc do Rego ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
Biologically Active ◽  
Mutant Mice ◽  
Insulin Production ◽  
Active Peptide ◽  
Important Regulator ◽  
Biologically Active Peptide ◽  
The Impact

AbstractIntroduction26RFa (QRFP) is a biologically active peptide that has been found to control feeding behaviour by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism.Research design and methods26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro-26RFa was replaced by the iCre sequence. Energy and glucose metabolism was evaluated through measurement of complementary parameters. Morphological and physiological alterations of the pancreatic islets were also investigated.ResultsOur data do not reveal significant alteration of energy metabolism in the 26RFa-deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa mutant mice exhibit an altered glycemic phenotype with an increased hyperglycemia after a glucose challenge associated with an impaired insulin production, and an elevated hepatic glucose production. 2D and 3D immunohistochemical experiments indicate that the insulin content of pancreatic β cells is much lower in the 26RFa-/- mice as compared to the wild-type littermates.ConclusionDisruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis with, in particular, a deficit in insulin production by the pancreatic islets. These findings further support the notion that 26RFa is an important regulator of glucose homeostasis.Significance of this studyWhat is already known about this subject?26RFa is a biologically active peptide produced in abundance in the gut and the pancreas. 26RFa has been found to regulate glucose homeostasis by acting as an incretin and by increasing insulin sensitivity.What are the new findings?Disruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis with, in particular, a deficit in insulin production by the pancreatic islets, assessing therefore the notion that 26RFa is an important regulator of glucose homeostasis.How might these results change the focus of research or clinical practice?Identification of a novel actor in the regulation of glucose homeostasis is crucial to better understand the general control of glucose metabolism in physiological and pathophysiological conditions, and opens new fields of investigation to develop innovative drugs to treat diabetes mellitus.

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