ArticleDiabetologia2011
Hypercholesterolaemia, signs of islet microangiopathy and altered angiogenesis precede onset of type 2 diabetes in the Goto-Kakizaki (GK) rat.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- A review of air pollution as a driver of cardiovascular disease risk across the diabetes spectrum.Frontiers in endocrinology · 2024Review
- Diversity of pathophysiology in type 2 diabetes shown by islet pathology.Journal of diabetes investigation · 2022Review
- Islet microangiopathy and augmented β-cell loss in Japanese non-obese type 2 diabetes patients who died of acute myocardial infarction.Journal of diabetes investigation · 2021Article
- Ocular surface complications in diabetes: The interrelationship between insulin and enkephalin.Biochemical pharmacology · 2021Review
- Vascular Endothelial Function as a Valid Predictor of Variations in Pulmonary Function in T2DM Patients Without Related Complications.Frontiers in endocrinology · 2021Article
- Endothelial Function Assessed by Digital Volume Plethysmography Predicts the Development and Progression of Type 2 Diabetes Mellitus.Journal of the American Heart Association · 2019Article
- Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus?PloS one · 2017Article
- Regenerating 1 and 3b gene expression in the pancreas of type 2 diabetic Goto-Kakizaki (GK) rats.PloS one · 2014Article
- Endothelial dysfunction in (pre)diabetes: characteristics, causative mechanisms and pathogenic role in type 2 diabetes.Reviews in endocrine & metabolic disorders · 2013Review
- Effects on high cholesterol-fed to liver, retina, hippocampus, and Harderian gland in Goto-Kakizaki rat.International journal of clinical and experimental pathology · 2013Article
- The use of animal models in diabetes research.British journal of pharmacology · 2012Article
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe adult non-obese Goto-Kakizaki (GK) rat model of type 2 diabetes, particularly females, carries in addition to hyperglycaemia a genetic predisposition towards dyslipidaemia, including hypercholesterolaemia. As cholesterol-induced atherosclerosis may be programmed in utero, we looked for signs of perinatal lipid alterations and islet microangiopathy. We hypothesise that such alterations contribute towards defective pancreas/islet vascularisation that might, in turn, lead to decreased beta cell mass. Accordingly, we also evaluated islet inflammation and endothelial activation in both prediabetic and diabetic animals.
methodsBlood, liver and pancreas were collected from embryonic day (E)21 fetuses, 7-day-old prediabetic neonates and 2.5-month-old diabetic GK rats and Wistar controls for analysis/quantification of: (1) systemic variables, particularly lipids; (2) cholesterol-linked hepatic enzyme mRNA expression and/or activity; (3) pancreas (fetuses) or collagenase-isolated islet (neonates/adults) gene expression using Oligo GEArray microarrays targeted at rat endothelium, cardiovascular disease biomarkers and angiogenesis, and/or RT-PCR; and (4) pancreas endothelial immunochemistry: nestin (fetuses) or von Willebrand factor (neonates).
resultsSystemic and hepatic cholesterol anomalies already exist in GK fetuses and neonates. Hyperglycaemic GK fetuses exhibit a similar percentage decrease in total pancreas and islet vascularisation and beta cell mass. Normoglycaemic GK neonates show systemic inflammation, signs of islet pre-microangiopathy, disturbed angiogenesis, collapsed vascularisation and altered pancreas development. Concomitantly, GK neonates exhibit elevated defence mechanisms. CONCLUSIONS/
interpretationThese data suggest an autoinflammatory disease, triggered by in utero programming of cholesterol-induced islet microangiopathy interacting with chronic hyperglycaemia in GK rats. During the perinatal period, GK rats show also a marked deficient islet vascularisation in conjunction with decreased beta cell mass.
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