Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice

Ayala, Julio E.; Samuel, Varman T.; Morton, Gregory J.; Obici, Silvana; Croniger, Colleen M.; Shulman, Gerald I.; Wasserman, David H.; McGuinness, Owen P.

doi:10.1242/dmm.006239

Cited by 619 publications

(631 citation statements)

References 60 publications

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“…However, it was not possible to obtain insulin-specific responses using the current experimental protocol, and indeed this is not trivial to achieve in different areas of the CNS. Interestingly, others have found that measurement of muscle (but not liver) insulin sensitivity varies with length of fasting before assessment [49], therefore it is conceivable that shorter periods of fasting could uncover differences in basal signalling, although we did maintain differences in fasting insulin during the 14 h fast. Taken together, our data argue against the development of major changes in basal insulin signalling pathways in the brain in response to HF feeding, and supports a CNS mechanism that is independent of insulin sensitivity underlying the loss of behavioural flexibility in the HF-fed animals.…”

Section: Discussionmentioning

confidence: 72%

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

et al. 2012

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Aims/hypothesis We previously demonstrated that animals fed a high-fat (HF) diet for 10 weeks developed insulin resistance and behavioural inflexibility. We hypothesised that intervention with metformin would diminish the HF-feedingevoked cognitive deficit by improving insulin sensitivity. Methods Rats were trained in an operant-based matching and non-matching to position task (MTP/NMTP). Animals received an HF (45% of kJ as lard; n024), standard chow (SC; n016), HF + metformin (144 mg/kg in diet; n020) or SC + metformin (144 mg/kg in diet; n016) diet for 10 weeks before retesting. Body weight and plasma glucose, insulin and leptin were measured. Protein lysates from various brain areas were analysed for alterations in intracellular signalling or production of synaptic proteins. Results HF-fed animals developed insulin resistance and an impairment in switching task contingency from matching to non-matching paradigm. Metformin attenuated the insulin resistance and weight gain associated with HF feeding, but had no effect on performance in either MTP or NMTP tasks. No major alteration in proteins associated with insulin signalling or synaptic function was detected in response to HF diet in the hypothalamus, hippocampus, striatum or cortex. Conclusions/interpretation Metformin prevented the metabolic but not cognitive alterations associated with HF feeding.The HF diet protocol did not change basal insulin signalling in the brain, suggesting that the brain did not develop insulin resistance. These findings indicate that HF diet has deleterious effects on neuronal function over and above those related to insulin resistance and suggest that weight loss may not be sufficient to reverse some damaging effects of poor diet.

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Section: Discussionmentioning

confidence: 72%

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

et al. 2012

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“…To test the efficacy of the liposome‐treated scaffold as transplantation site for islets, 800 rat islets were implanted in scaffolds treated with liposomes loaded with 0.5 and 1.0 μg growth factor and compared with untreated controls. Nonfasting blood glucose levels of the mice were monitored three times a week and 2 weeks after transplantation an intraperitoneal glucose tolerance test (IPGTT) was performed 29. Islet function was monitored for 75 days after islet transplantation.…”

Section: Methodsmentioning

confidence: 99%

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Smink

Swart

et al. 2017

J Biomedical Materials Res

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The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by applying liposomes for controlled release of angiogenic factors. The angiogenic capacity of platelet‐derived growth factor, vascular endothelial growth factor, acidic fibroblast growth factor (aFGF), and basic FGF were compared in a tube formation assay. Furthermore, the release kinetics of different liposome compositions were tested. aFGF and L‐α‐phosphatidylcholine/cholesterol liposomes were selected to support vascularization. Two dosages of aFGF‐liposomes (0.5 and 1.0 μg aFGF per injection) were administered weekly for a month after which islets were transplanted. We observed enhanced efficacy in the immediate post‐transplant period compared to the untreated scaffolds. However, on the long‐term, glucose levels of the aFGF treated animals started to increase to diabetic levels. These results suggest that injections with aFGF liposomes do improve vascularization and the immediate restoration of blood glucose levels but does not facilitate the long‐term survival of islets. Our data emphasize the need for long‐term studies to evaluate potential beneficial and adverse effects of vascularization protocols of scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2533–2542, 2017.

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“…glucose tolerance test was performed following 8 weeks of HF diet feeding, as described previously. 24 In brief, mice were fasted overnight for 16 hours. The test was performed in a quiet room, preheated to +30°C.…”

Section: Glucose Curvementioning

confidence: 99%

Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Palomera-Ávalos

Griñán-Ferré

Izquierdo

et al. 2017

Rejuvenation Research

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Inflammation and oxidative stress (OS) are key points in age progression. Both processes impact negatively in cognition and in brain functions. Resveratrol (RV) has been postulated as a potent antioxidant natural compound, with rejuvenating properties. Inducing a metabolic stress by high-fat (HF) diet in aged C56/BL6 (24 months) led to cognitive disturbances compared with control age mated and with young mice. These changes were prevented by RV. Molecular determinations demonstrated a significant increase in some inflammatory parameters (TNF-a, Cxcl10, IL-1, IL-6, and Ccl3) in old mice, but slight changes in OS machinery. RV mainly induced the recovery of the metabolically stressed animals. The study of key markers involved in senescence and rejuvenation (mitochondrial biogenesis and Sirt1-AMPK-PGC1-a) demonstrated that RV is also able to modulate the changes in these cellular metabolic pathways. Moreover, changes of epigenetic marks (methylation and acetylation) that are depending on OS were demonstrated. On the whole, results showed the importance of integrative role of different cellular mechanisms in the deleterious effects of age in cognition and the beneficial role of RV. The work presented in this study showed a wide range of processes modified in old age and by metabolic stress, weighting the importance of each one and the role of RV as a possible strategy for fighting against.

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Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice

Cited by 619 publications

References 60 publications

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

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