Modulation of dopamine receptor supersensitivity by chronic insulin: implication in schizophrenia

Lozovsky, David; Kopin, Irwin J.; Saller, Charles

doi:10.1016/0006-8993(85)91178-3

Cited by 20 publications

(10 citation statements)

References 22 publications

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“…For instance, it has been demonstrated that insulin can reverse the haloperidolinduced increase in dopamine receptors, but insulin alone does not have any significant effect on dopamine receptor density [210]. Consistently, increase in dopamine receptors in diabetic rats has also been reported [211].…”

Section: Insulin and Neurotransmissionsupporting

confidence: 59%

Insulin in the Brain: Sources, Localization and Functions

et al. 2012

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Historically, insulin is best known for its role in peripheral glucose homeostasis, and insulin signaling in the brain has received less attention. Insulin-independent brain glucose uptake has been the main reason for considering the brain as an insulin-insensitive organ. However, recent findings showing a high concentration of insulin in brain extracts, and expression of insulin receptors (IRs) in central nervous system tissues have gathered considerable attention over the sources, localization, and functions of insulin in the brain. This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation. This review also considers the neuromodulatory and neurotrophic effects of insulin, resulting in proliferation, differentiation, and neurite outgrowth, introducing insulin as an attractive tool for neuroprotection against apoptosis, oxidative stress, beta amyloid toxicity, and brain ischemia.

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Section: Insulin and Neurotransmissionsupporting

confidence: 59%

Insulin in the Brain: Sources, Localization and Functions

et al. 2012

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“…While it fell into disfavor for several reasons, its effectiveness in some patients has never been understood fully. It is significant, however, that recent animal studies suggest the mechanisms of insulin therapy action may include modulation of dopamine neurotransmission in a manner similar to that produced by typical neuroleptic medications [Lozovsky et al, 1985]. Moreover, numerous studies report either impaired glucose tolerance or increased resistance to insulin in schizophrenia [e.g., Braceland et al, 1945;Franzen and Nilsson, 1968;Schimmelbusch et al, 1971;Brambilla et al, 1976], or relationships between fasting levels of glucose or insulin, and abnormal movements or tardive dyskinesia [Ganzini et al, 1991;Schultz et al, 1999].…”

Section: Introductionmentioning

confidence: 98%

Evidence for linkage between regulatory enzymes in glycolysis and schizophrenia in a multiplex sample

Stone

Faraone

et al. 2003

American J of Med Genetics Pt B

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Observations of impaired glucose regulation in schizophrenia are long-standing, although their pathological and etiological significance is uncertain. One approach to the issue that minimizes environmental variables (e.g., medication and diet) is to determine whether genes related to glucose regulation show genetic linkage to schizophrenia. We examined the potential role of glucose metabolism in schizophrenia through a genome scan of affection status in schizophrenia and an empirical method for deriving P-values. Data were utilized from the NIMH Genetics Initiative for Schizophrenia dataset, which comprises a total sample consisting of 71 pedigrees containing 218 nuclear families and 987 individuals. A genome scan with 459 markers spaced at an average of 10 cM intervals was conducted using the linkage analysis program Genehunter separately for European- and African-American groups. Enzymes that regulate glycolysis were identified and the genes regulating these enzymes were located through the Online Mendelian Inheritance in Man (OMIM) website. The focus in this study was on genes located near previously reported schizophrenia susceptibility regions. The genome-wide significance of these genes to schizophrenia was assessed using permutation testing. When results were adjusted for multiple testing within and across ethnic groups, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2; chromosome 1q32.2) achieved genome-wide significance (P = 0.04). In addition, hexokinase 3 (HK3; chromosome 5q35.3) was also suggestive of linkage (P = 0.09). For the European-American sample, PFKFB2 (1q32.2), hexokinase 3 (HK3; 5q35.3), and pyruvate kinase 3 (PK3; chromosome 15q23) achieved significance at the 0.05 level. None of the genes showed significance in the African-American sample. Our results provide further support for the view that genes that regulate glucose metabolism may also influence susceptibility to schizophrenia. More generally, they support the view that relationships between glucose dysregulation and schizophrenia are inherent to the disorder, and are not merely epiphenomena related to medication or other treatment factors.

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“…Experimentally induced diabetes in rodents led to a 35% increase in dopamine receptor binding in the striatum (Lozoversusky et al 1981). Conversely, rats treated with insulin failed to exhibit an increase in the number of striatal dopamine receptors that typically occurs with chronic exposure to haloperidol (Lozoversusky et al 1985).…”

Section: Introductionmentioning

confidence: 98%