Animal models of non‐insulin‐dependent diabetes

Shafrir, Eleazar

doi:10.1002/dmr.5610080302

Cited by 159 publications

(95 citation statements)

References 161 publications

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“…These results are very similar to those previously reported in spontaneously occurring obese type 2 diabetes mellitus model mice [2,11,12]. It was confirmed that the 54-week-old ICR-MSG males had maintained a type 2 diabetes mellitus condition for a long period because they showed the same symptoms of obesity, hyperglycemia, hyperinsulinemia, hypertrophy of pancreatic islets, and anomalous lipid value they had at 29 weeks of age.…”

Section: Discussionsupporting

confidence: 90%

Type 2 Diabetes Mellitus in Obese Mouse Model Induced by Monosodium Glutamate

et al. 2006

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Section: Discussionsupporting

confidence: 90%

Type 2 Diabetes Mellitus in Obese Mouse Model Induced by Monosodium Glutamate

et al. 2006

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“…those located in the locus Nidd/SJL. These data further confirm the validity of the concept that Type II diabetes in rodents ('diabesity') is produced by the combination of obesity and diabetes genes [6,10,11,12], and that it closely resembles the human disease.…”

Section: Discussionsupporting

confidence: 80%

Characterisation of the mouse diabetes susceptibility locus Nidd/SJL: islet cell destruction, interaction with the obesity QTL Nob1, and effect of dietary fat

Plum¹,

Giesen²,

Kluge

et al. 2002

Diabetologia

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Aims/hypothesis. The diabetes susceptibility locus Nidd/SJL was identified in an outcross of New Zealand obese (NZO) and lean Swiss/Jackson Laboratory mouse strain (SJL) mice. Here we characterise its effects in a NZO × F1(SJL×NZO) backcross population raised on high-fat or standard diet, and describe its interaction with the obesity quantitative trait locus (QTL) Nob1. Methods. NZO × F1(SJL×NZO) backcross mice were raised on a normal or high fat diet and were monitored (body weight, blood glucose, serum insulin) for 22 weeks. Genotypes of polymorphic markers were determined by PCR, and linkage analysis was done. Pancreas morphology was assessed by conventional staining and immunohistochemistry of insulin. Results. In backcross mice raised on a high-fat diet, Nidd/SJL produced hyperglycaemia (maximum likelihood of the odds (LOD) score 9.9), hypoinsulinaemia, reduction of islet-cell volume, and loss of beta cells. No effect was observed on body weight and serum insulin concentrations before the onset of hyperglycaemia. The development of diabetes in carriers of Nidd/SJL was markedly accelerated and aggravated by the obesity/hyperinsulinaemia QTL Nob1; together, these loci were responsible for approximately 90% of the diabetes observed in the backcross population. When raised on a standard diet, Nidd/SJL carriers exhibited a fivefold higher prevalence of diabetes, but Nob1 failed to enhance the effect of Nidd/SJL. Conclusion/interpretation. Diabetes in this obese mouse model is the result of an interaction of genes responsible for obesity/insulin resistance (e.g. Nob1) and islet cell failure (Nidd/SJL). The combined diabetogenic effects of Nidd/SJL and Nob1 were markedly enhanced by a high-fat diet, whereas that of Nidd/SJL alone was independent of the dietary fat content. [Diabetologia (2002) 45:823-830]

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“…db/db Mice display obesity and type 2 diabetes, due to the absence of functional leptin receptors, the main activator of STAT3 in pancreatic b-cells (Shafrir 1992, Morton et al 1999. We have demonstrated that adult pancreatic islets, cultured with PRL, show an upregulation in STAT3 gene expression .…”

Section: Cmentioning

confidence: 80%

Signal transducer and activator of transcription 3-regulated sarcoendoplasmic reticulum Ca2+-ATPase 2 expression by prolactin and glucocorticoids is involved in the adaptation of insulin secretory response during the peripartum period

Anhê

Nogueira

Nicoletti-Carvalho

et al. 2007

Journal of Endocrinology

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During pregnancy, the maternal endocrine pancreas undergoes, as a consequence of placental lactogens and prolactin (PRL) action, functional changes that are characterized by increased glucose-induced insulin secretion. After delivery, the maternal endocrine pancreas rapidly returns to nonpregnant state, which is mainly attributed to the increased serum levels of glucocorticoids (GCs). Although GCs are known to decrease insulin secretion and counteract PRL action, the mechanisms for these effects are poorly understood. We have previously demonstrated that signal transducer and activator of transcription 3 (STAT3) is increased in islets treated with PRL. In the present study, we show that STAT3 expression and serine phosphorylation are increased in pancreatic islets at the end of pregnancy (P19). STAT3 serine phosphorylation rapidly returned to basal levels 3 days after delivery (L3). The expression of the sarcoendoplasmic reticulum Ca 2C -ATPase 2 (SERCA2), a crucial protein involved in the regulation of calcium handling in b-cells, was also increased in P19, returning to basal levels at L3. PRL increased SERCA2 and STAT3 expressions and STAT3 serine phosphorylation in RINm5F cells. The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. Moreover, PRL-induced STAT3 serine phosphorylation and SERCA2 expression were inhibited by dexamethasone (DEX). Insulin secretion from islets of P19 rats pre-incubated with thapsigargin and L3 rats showed a dramatic suppression of first phase of insulin release. The present results indicate that PRL regulates SERCA2 expression by a STAT3-dependent mechanism. PRL effect is counteracted by DEX and might contribute to the adaptation of maternal endocrine pancreas during the peripartum period.

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Animal models of non‐insulin‐dependent diabetes

Cited by 159 publications

References 161 publications

Type 2 Diabetes Mellitus in Obese Mouse Model Induced by Monosodium Glutamate

Type 2 Diabetes Mellitus in Obese Mouse Model Induced by Monosodium Glutamate

Characterisation of the mouse diabetes susceptibility locus Nidd/SJL: islet cell destruction, interaction with the obesity QTL Nob1, and effect of dietary fat

Signal transducer and activator of transcription 3-regulated sarcoendoplasmic reticulum Ca2+-ATPase 2 expression by prolactin and glucocorticoids is involved in the adaptation of insulin secretory response during the peripartum period

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