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

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.

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

Growth Factors ◽

10.3109/08977190903199074 ◽

2009 ◽

Vol 27 (6) ◽

pp. 409-418 ◽

Cited By ~ 3

Author(s):

Elisa Fernández-Millán ◽

Marie Noëlle Gangnerau ◽

Laura De Miguel-Santos ◽

Sophie Calderari ◽

Patricia Serradas ◽

...

Keyword(s):

Beta Cell ◽

Cell Mass ◽

Beta Cell Mass ◽

Gk Rat

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

Biomolecules ◽

10.3390/biom11020179 ◽

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.

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