Abstract Both endocannabinoids and insulin regulate peripheral and cerebral glucose homeostasis via convergent signaling pathways that are impacted by diabetes. Here we asked how glucose metabolism and important facets of insulin signaling are affected in the forebrain of cannabinoid CB1 receptor knockout mice (CB1R-KO) and their wild-type (WT) littermates, seven weeks after the induction of insulinopenia/hyperglycemia (diabetes) with intraperitoneal streptozotocin injection. Sham-injected animals served as control. Diabetes caused milder weight loss in the WT mice compared to the phenotypically ˜11% leaner CB1R-KO, while hyperglycemia was similar. Resting [3H]deoxyglucose uptake was significantly reduced by ˜20% in acute ex vivo frontocortical and hippocampal slices obtained from both the sham-injected CB1R-KO and the diabetic WT mice. Surprisingly, the third cohort, the diabetic CB1R-KO showed no further impairment in glucose uptake, as compared to the sham-injected CB1R-KO. Depolarization-induced [3H]deoxyglucose uptake was proportional to the respective resting values only in the cortex in all four cohorts. The dissipative metabolism of [14C]-U-glucose remained largely unaffected in all cohorts of animals. However, diabetes reduced cortical CB1R density by ˜20%, as assessed by Western blotting. Albeit the changes in insulin signaling did not reflect the glucose uptake profile in each cohort, there were significant interactions between diabetes and genotype. In conclusion, a chronic decrease or lack of CB1R expression reduces glucose uptake in the mouse brain. Additionally, diabetes failed to cause further impairment in cerebral glucose uptake in the CB1R-KO. These suggest that diabetic encephalopathy may be in part associated with lower CB1R expression.
Last. Andras Hajnal(PSU: Pennsylvania State University)H-Index: 35
view all 5 authors...
Abstract Depression is associated with uncontrolled diabetes, which indicates a lack of insulin effect, yet the role of the insulin receptor in mediating depression is not clearly established because insulin receptors are not required for glucose entry into the brain. However, insulin receptors are important for brain function since insulin receptor knockout mice have depressive-like activity. Depression and cognitive problems are also associated with low insulin-like growth factor-1 (IGF-1) in ...
Last. Ewan C. McNay(University at Albany, SUNY)H-Index: 34
view all 4 authors...
Abstract The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased...
Hypometabolism, characterized by decreased brain glucose consumption, is a common feature of many neurodegenerative diseases. Initial hypometabolic brain state, created by characteristic risk factors, may predispose the brain to acquired epilepsy and sporadic Alzheimer's and Parkinson's diseases, which are the focus of this review. Analysis of available data suggests that deficient glucose metabolism is likely a primary initiating factor for these diseases, and that resulting neuronal dysfunctio...
#1Tony Jourdan(NIH: National Institutes of Health)H-Index: 18
#2Sarah M. Nicoloro(UMMS: University of Massachusetts Medical School)H-Index: 23
Last. George Kunos(NIH: National Institutes of Health)H-Index: 86
view all 12 authors...
Abstract Objective Obesity-induced accumulation of ectopic fat in the liver is thought to contribute to the development of insulin resistance, and increased activity of hepatic CB 1 R has been shown to promote both processes. However, lipid accumulation in liver can be experimentally dissociated from insulin resistance under certain conditions, suggesting the involvement of additional mechanisms. Obesity is also associated with pro-inflammatory changes which, in turn, can promote insulin resista...
Last. Péter Hermann(Semmelweis University)H-Index: 12
view all 9 authors...
Abstract Since a significant proportion of diabetic patients have clinical or subclinical neuropathy, there may be concerns about the use of local anaesthetics. The present study was designed to determine and compare the effects of articaine, a widely used anaesthetic in dental practice, and lidocaine on the resting and axonal stimulation-evoked release of [3H]noradrenaline ([3H]NA) in prefrontal cortex slices and the release of [3H]NA in spinal cord slices prepared from non-diabetic and strepto...
BACKGROUND & OBJECTIVE: Cannabis is one of the earliest cultivated plants. Cannabis of industrial utility and culinary value is generally termed as hemp. Conversely, cannabis that is bred for medical, spiritual and recreational purposes is called marijuana. The female marijuana plant produces a significant quantity of bio- and psychoactive phytocannabinoids, which regained the spotlight with the discovery of the endocannabinoid system of the animals in the early 90's. Nevertheless, marijuana is ...
The type-1 cannabinoid receptor (CB1) is the main effector of the endocannabinoid system (ECS), which is involved in most brain and body functions. In this Perspective, we provide evidence indicating that CB1 receptor functions are key determinants of bodily coordinated exostatic processes. First, we will introduce the concepts of endostasis and exostasis as compensation or accumulation for immediate or future energy needs and discuss how exostasis has been necessary for the survival of species ...
We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression l...
Classical views posit G protein-coupled cannabinoid receptor 1s (CB1Rs) at the cell surface with cytosolic Giα-mediated signal transduction. Hebert-Chatelain et al. (2016) instead place CB1Rs at mitochondria limiting neuronal respiration by soluble adenylyl cyclase-dependent modulation of complex I activity. Thus, neuronal bioenergetics link to synaptic plasticity and, globally, learning and memory.
BACKGROUND The cannabinoid receptor type-1 (CB1R) is a major regulator of metabolism, growth and inflammation. Yet, its potential role in the skin is not well understood. Our aim was to evaluate the role of CB1R in aging-like diabetic skin changes by using a CB1R knockout mouse model. METHODS We evaluated several signals of skin aging in wild-type control (WT), WT streptozotocin-induced type 1 diabetic mice (WT DM), CB1R knockout (CB1RKO) and CB1RKO DM mice. We quantified markers of inflammation...
Last. Miguel Huerta(University of Colima)H-Index: 17
view all 10 authors...
Previous studies have suggested a role of the endocannabinoid system in metabolic diseases, such as diabetes. We investigated the effect of diabetes on cannabinoid receptor type 1 (CB1) expression and cannabinoid-induced vasorelaxation in rat aorta rings. Aortas from healthy rats and from rats with experimentally induced diabetes were used to compare the vasorelaxant effect of the cannabinoid agonist arachidonylcyclopropylamide (ACPA) and CB1 expression and localization. After 4–8 weeks of diabe...
Last. Attila Köfalvi(UC: University of Coimbra)H-Index: 24
view all 17 authors...
Abstract Here we aimed to unify some previous controversial reports on changes in both cannabinoid CB1 receptor (CB1R) expression and glucose metabolism in the forebrain of rodent models of diabetes. We determined how glucose metabolism and its modulation by CB1R ligands evolve in the frontal cortex of young adult male Wistar rats, in the first 8 weeks of streptozotocin-induced type-1 diabetes (T1D). We report that frontocortical CB1R protein density was biphasically altered in the first month o...
Abstract Background Cannabinoid receptor 1 (CB1) identification by western blot (WB) has generated a great deal of controversial data making the interpretation of the results difficult. Our purpose is to find the most adequate experimental conditions to detect CB1 by WB and immunoprecipitation (IP) as a first step towards the study of CB1 interactome. New method We use CB1 knockout mice tissue as negative controls and describe appropriate sample handling conditions for CB1 detection by WB and IP...