Preproinsulin I and II mRNAs and insulin electron microscopic immunoreaction are present within the rat fetal nervous system

Schechter, Ruben; Beju, Delia; Gaffney, Tim; Schaefer, Fred; Whetsell, L

doi:10.1016/0006-8993(96)00664-6

Cited by 88 publications

(29 citation statements)

References 18 publications

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“…Published data support the possibility that there is a local production of insulin in the brain, although this remains a point of controversy (Gerozissis 2003(Gerozissis , 2004(Gerozissis , 2008Schechter et al 1996). Numerous peptides involved in energy homeostasis, produced mainly in the periphery, are also expressed in the central nervous system (Gerozissis 2008;Wilkinson et al 2007).…”

Section: Discussionmentioning

confidence: 92%

“…Numerous peptides involved in energy homeostasis, produced mainly in the periphery, are also expressed in the central nervous system (Gerozissis 2008;Wilkinson et al 2007). In various studies, insulin messenger RNA has been identified in the brain (Gerozissis 2008;Grunblatt et al 2007;Schechter et al 1996). In addition, alteration of insulin gene expression has been noted in pathologic situations, in particular in Alzheimer's disease (Grunblatt et al 2007;Steen et al 2005).…”

Section: Discussionmentioning

confidence: 98%

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A Dietary Fat Excess Alters Metabolic and Neuroendocrine Responses Before the Onset of Metabolic Diseases

et al. 2008

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Early changes in neuroendocrine pathways are essential in the development of metabolic pathologies. Thus, it is important to have a better understanding of the signals involved in their initiation. Long-term consumption of high-fat diets induces insulin resistance, obesity, diabetes. Here, we have investigated early neural and endocrine events in the hypothalamus and hippocampus induced by a short-term high fat, low carbohydrate diet in adult male Wistar rats. The release of serotonin, which is closely associated with the actions of insulin and leptin, was measured, by electrochemical detection following reverse-phase liquid chromatography (HPLC), in the extracellular space of the medial hypothalamus and the dorsal hippocampus in samples obtained from non-anesthetized animals, by microdialysis. The high-fat diet had a specific effect on the hypothalamus. Serotonin release induced by food intake was reduced after 1 week, and effectively ceased after 6 weeks of the diet. After 1 week, there was an increased gene expression of the insulin receptor and the insulin receptor substrates IRS1 and IRS2, as measured by real-time PCR. After 6 weeks of diet, insulin gene expression increased. Leptinemia increased in all cases. This new data support the concept that high-fat diets, in addition to have peripheral effects, cause a rapid alteration in specific central mechanisms involved in energy and glucose homeostasis. The changes in the gene expression of insulin and signaling elements represent possible adaptations aimed at counterbalancing the reduced responsiveness of the serotonergic system to nutritional signals and maintaining homeostasis.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 98%

A Dietary Fat Excess Alters Metabolic and Neuroendocrine Responses Before the Onset of Metabolic Diseases

et al. 2008

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“…A smaller proportion of de novo INS gene expression and synthesis in the brain has been demonstrated in immature and mature neuronal cells rather than glial cells [30][31][32]. Insulin mRNA was dispersed in a highly specific pattern with the highest density in pyramidal cells of the hippocampus and a high density in the medial prefrontal cortex, entorhinal cortex, perirhinal cortex, thalamus, granule cell layer of the olfactory bulb, and hypothalamus [32,33].…”

Section: Discussionmentioning

confidence: 99%

Insulin/IGF Signaling-Related Gene Expression in the Brain of a Sporadic Alzheimer's Disease Monkey Model Induced by Intracerebroventricular Injection of Streptozotocin

Lee

Kim

Park

et al. 2013

JAD

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We reported previously that the intracerebroventricular streptozotocin (icv-STZ)-treated cynomolgus monkey showed regionally specific glucose hypometabolism in FDG-PET imaging, similar to that observed in the early stages of sporadic Alzheimer's disease (sAD). However, further pathological analyses of this model at the molecular level are needed to validate it as a feasible model for sAD. Two cynomolgus monkeys were injected with 2 mg/kg STZ into the cerebellomedullary cistern at day 1, 7 and 14. Two control monkeys were given normal saline. At 5 months after injection, the expression levels of genes encoding 9 upstream molecules in insulin/insulin-like growth factor (IGF) signaling and markers for 4 cell-type populations in the frontal cortex, hippocampus, posterior cingulate, precuneus, and occipital cortex of control and icv-STZ treated cynomolgus monkeys were examined. Real-time quantitative PCR analyses demonstrated that the overall mRNA expression of insulin/IGF signaling-related genes was mainly impaired in the anterior part of the cerebrum, frontal cortex, and hippocampus, similar to the early stage of sAD. The changes were accompanied by the loss of oligodendrocytes and neurons. The posterior part of the cerebrum did not show degenerative alterations. The present study provides important fundamental information on the icv-STZ monkey model for sAD. These results may help guide future studies using this model for the investigation of pathological mechanisms and the development of drugs for sAD.

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“…Neurons themselves express insulin [30,31], but the majority of the brain insulin originates from the periphery through the blood–brain barrier via a saturable transport mechanism [32]. A role for insulin dysfunction in AD has been postulated [33–37].…”

Section: Discussionmentioning

confidence: 99%

Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes

Liu

Grundke‐Iqbal

et al. 2011

The Journal of Pathology

435

337

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Brain glucose metabolism is impaired in Alzheimer’s disease (AD), the most common form of dementia. Type 2 diabetes mellitus (T2DM) is reported to increase the risk for dementia, including AD, but the underlying mechanism is not understood. Here, we investigated the brain insulin–PI3K–AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM–AD and seven control cases. We found decreases in the levels and activities of several components of the insulin–PI3K–AKT signalling pathway in AD and T2DM cases. The deficiency of insulin–PI3K–AKT signalling was more severe in individuals with both T2DM and AD (T2DM–AD). This decrease in insulin–PI3K–AKT signalling could lead to activation of glycogen synthase kinase-3β, the major tau kinase. The levels and the activation of the insulin–PI3K–AKT signalling components correlated negatively with the level of tau phosphorylation and positively with protein O-GlcNAcylation, suggesting that impaired insulin–PI3K–AKT signalling might contribute to neurodegeneration in AD through down-regulation of O-GlcNAcylation and the consequent promotion of abnormal tau hyperphosphorylation and neurodegeneration. The decrease in brain insulin–PI3K–AKT signalling also correlated with the activation of calpain I in the brain, suggesting that the decrease might be caused by calpain over-activation. Our findings provide novel insight into the molecular mechanism by which type 2 diabetes mellitus increases the risk for developing cognitive impairment and dementia in Alzheimer’s disease.

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Preproinsulin I and II mRNAs and insulin electron microscopic immunoreaction are present within the rat fetal nervous system

Cited by 88 publications

References 18 publications

A Dietary Fat Excess Alters Metabolic and Neuroendocrine Responses Before the Onset of Metabolic Diseases

A Dietary Fat Excess Alters Metabolic and Neuroendocrine Responses Before the Onset of Metabolic Diseases

Insulin/IGF Signaling-Related Gene Expression in the Brain of a Sporadic Alzheimer's Disease Monkey Model Induced by Intracerebroventricular Injection of Streptozotocin

Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes

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