scholarly journals Effect of Postnatal Nutritional Environment Due to Maternal Diabetes on Beta Cell Mass Programming and Glucose Intolerance Risk in Male and Female Offspring

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 179
Author(s):  
Danièle Bailbe ◽  
Junjun Liu ◽  
Pengfei Gong ◽  
Bernard Portha
Keyword(s):  
Beta Cell ◽  
Glucose Intolerance ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Maternal Diabetes ◽  
Postnatal Life ◽  
Gk Rat ◽  
Foster Mothers ◽  
The Impact

Besides the fetal period, the suckling period is a critical time window in determining long-term metabolic health. We undertook the present study to elucidate the impact of a diabetic suckling environment alone or associated with an in utero diabetic environment on beta cell mass development and the risk of diabetes in the offspring in the long term. To that end, we have compared two experimental settings. In setting 1, we used Wistar (W) rat newborns resulting from W ovocytes (oW) transferred into diabetic GK rat mothers (pGK). These oW/pGK neonates were then suckled by diabetic GK foster mothers (oW/pGK/sGK model) and compared to oW/pW neonates suckled by normal W foster mothers (oW/pW/sW model). In setting 2, normal W rat newborns were suckled by diabetic GK rat foster mothers (nW/sGK model) or normal W foster mothers (nW/sW model). Our data revealed that the extent of metabolic disorders in term of glucose intolerance and beta cell mass are similar between rats which have been exposed to maternal diabetes both pre- and postnatally (oW/pGK/sGK model) and those which have been exposed only during postnatal life (nW/sW model). In other words, being nurtured by diabetic GK mothers from birth to weaning was sufficient to significantly alter the beta cell mass, glucose-induced insulin secretion and glucose homeostasis of offspring. No synergistic deleterious effects of pre-and postnatal exposure was observed in our setting.

PS15 - 3. Long-term ketogenic diet leads to weight gain, glucose intolerance and reduced beta-cell mass in mice

2013 ◽  
Vol 11 (4) ◽  
pp. 189-189
Author(s):  
Johanne H. Ellenbroek ◽  
Laura van Dijck ◽  
Hendrica A. Töns ◽  
Ton J. Rabelink ◽  
Françoise Carlotti ◽  
...  
Keyword(s):  
Weight Gain ◽  
Beta Cell ◽  
Ketogenic Diet ◽  
Glucose Intolerance ◽  
Cell Mass ◽  
Beta Cell Mass

Glucokinase Inactivation Paradoxically Ameliorates Glucose Intolerance by Increasing Beta-Cell Mass in db/db Mice

Diabetes ◽  
2021 ◽  
pp. db200881
Author(s):  
Kazuno Omori ◽  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Yuki Yamauchi ◽  
Shinichiro Kawata ◽  
...  
Keyword(s):  
Beta Cell ◽  
Glucose Intolerance ◽  
Cell Mass ◽  
Beta Cell Mass

scholarly journals Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Lukáš Alán ◽  
Tomáš Olejár ◽  
Monika Cahová ◽  
Jaroslav Zelenka ◽  
Zuzana Berková ◽  
...  
Keyword(s):  
Beta Cell ◽  
Wistar Rats ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Cell Physiology ◽  
Gk Rat ◽  
Cell Hyperplasia ◽  
Gk Rats ◽  
Delta Cell ◽  
Delta Cells

Reduced beta cell mass in pancreatic islets (PI) of Goto-Kakizaki (GK) rats is frequently observed in this diabetic model, but knowledge on delta cells is scarce. Aiming to compare delta cell physiology/pathology of GK to Wistar rats, we found that delta cell number increased over time as did somatostatin mRNA and delta cells distribution in PI is different in GK rats. Subtle changes in 6-week-old GK rats were found. With maturation and aging of GK rats, disturbed cytoarchitecture occurred with irregular beta cells accompanied by delta cell hyperplasia and loss of pancreatic polypeptide (PPY) positivity. Unlike the constant glucose-stimulation index for insulin PI release in Wistar rats, this index declined with GK age, whereas for somatostatin it increased with age. A decrease of GK rat PPY serum levels was found. GK rat body weight decreased with increasing hyperglycemia. Somatostatin analog octreotide completely blocked insulin secretion, impaired proliferation at low autocrine insulin, and decreased PPY secretion and mitochondrial DNA in INS-1E cells. In conclusion, in GK rats PI, significant local delta cell hyperplasia and suspected paracrine effect of somatostatin diminish beta cell viability and contribute to the deterioration of beta cell mass. Altered PPY-secreting cells distribution amends another component of GK PI’s pathophysiology.

Undernutrition of the GK rat during gestation improves pancreatic IGF-2 and beta-cell mass in the fetuses

2009 ◽  
pp. 1-1
Author(s):  
Elisa Fernandez-Millan ◽  
Marie Noëlle Gangnerau ◽  
Laura De Miguel-Santos ◽  
Sophie Calderari ◽  
Patricia Serradas ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Gk Rat

scholarly journals Postnatal activation of hypoxia pathway disrupts β-cell functional maturation

2021 ◽  
Author(s):  
Juxiang Yang ◽  
Batoul Hammoud ◽  
Abigail Ridler ◽  
Amanda M Ackermann ◽  
Kyoung-Jae Won ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Proliferation ◽  
Rat Pups ◽  
Functional Maturation ◽  
The Impact ◽  
Glucose Threshold

Objective: Hypoxic injuries occurring during the perinatal period can lead to persistent hyperinsulinism and profound hypoglycemia in newborns. We studied the impact of hypoxia-inducible pathway on the postnatal beta-cell function. Methods: Rat pups were treated daily between postnatal day (P)7 to P10 with adaptaquin (AQ), an inhibitor of prolyl hydroxylases, leading to stabilization of hypoxia-inducible factor 1A (HIF1A). In parallel, mouse pups were placed in a hypoxic chamber between embryonic day (E)19 to P6. Dynamic insulin secretion was assessed in both models by islet perifusions. Changes in gene expression were assessed by whole-islet RNA sequencing. Results: AQ-treated rat pups and hypoxic mouse pups were hypoglycemic and had higher levels of serum insulin. The AQ-/hypoxia-treated islets showed a decreased glucose threshold for insulin secretion compared to controls, indicative of a delay in beta-cell postnatal functional maturation. Islet morphometric analysis in the AQ-treated pups showed an increase in insulin area per pancreas, but no change in the number of islets or in the number of beta-cells per islet, consistent with a higher average size of beta-cells. Differential transcriptomic analysis showed upregulation of the expected HIF1A target genes. AQ-treated rat pups had decreased expression of cell cycle genes and decreased numbers of proliferating beta;-cells. Conclusion: We showed that hypoxia and pharmacologic activation of the hypoxia inducible pathway in early postnatal period leads to hyperinsulinism, due to the persistence of a low glucose threshold for insulin secretion. This exaggerated activation of hypoxia pathway also decreased early postnatal beta-cell proliferation, suggesting it can impact adult beta-cell mass and diabetes risk.

scholarly journals Beta Cell Imaging—From Pre-Clinical Validation to First in Man Testing

2020 ◽  
Vol 21 (19) ◽  
pp. 7274
Author(s):  
Stephane Demine ◽  
Michael L. Schulte ◽  
Paul R. Territo ◽  
Decio L. Eizirik
Keyword(s):  
Beta Cell ◽  
Cell Imaging ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Cell Loss ◽  
New Drugs ◽  
Clinical Validation ◽  
Beta Cell Imaging ◽  
The Impact

There are presently no reliable ways to quantify human pancreatic beta cell mass (BCM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. Furthermore, the lack of beta cell imaging hampers the evaluation of the impact of new drugs aiming to prevent beta cell loss or to restore BCM in diabetes. We presently discuss the potential value of BCM determination as a cornerstone for individualized therapies in diabetes, describe the presently available probes for human BCM evaluation, and discuss our approach for the discovery of novel beta cell biomarkers, based on the determination of specific splice variants present in human beta cells. This has already led to the identification of DPP6 and FXYD2γa as two promising targets for human BCM imaging, and is followed by a discussion of potential safety issues, the role for radiochemistry in the improvement of BCM imaging, and concludes with an overview of the different steps from pre-clinical validation to a first-in-man trial for novel tracers.

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