Article

The central insulin system and energy balance.

Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, OH 45237, USA.
Handbook of experimental pharmacology 01/2012; DOI: 10.1007/978-3-642-24716-3_5
Source: PubMed

ABSTRACT Insulin acts throughout the body to reduce circulating energy and to increase energy storage. Within the brain, insulin produces a net catabolic effect by reducing food intake and increasing energy expenditure; this is evidenced by the hypophagia and increased brown adipose tissue sympathetic nerve activity induced by central insulin infusion. Reducing the activity of the brain insulin system via administration of insulin antibodies, receptor antisense treatment, or receptor knockdown results in hyperphagia and increased adiposity. However, despite decades of research into the role of central insulin in food intake, many questions remain to be answered, including the underlying mechanism of action.

Download full-text

Full-text

Available from: Denovan Patrick Begg, Dec 10, 2014
1 Follower
 · 
131 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin acts within the central nervous system to regulate food intake and sympathetic nerve activity (SNA). Strong evidence indicates that glucocorticoids impair insulin-mediated glucose uptake and food intake. However, few data are available regarding whether glucocorticoids also modulate the sympathoexcitatory response to insulin. Therefore, the present study first confirmed that chronic administration of glucocorticoids attenuated insulin-induced increases in SNA and then investigated whether these effects were attributed to deficits in central insulin-mediated responses. Male Sprague-Dawley rats were given access to water or a drinking solution of the glucocorticoid agonist dexamethasone (0.3 μg/mL) for 7 days. A hyperinsulinemic-euglycemic clamp significantly increased lumbar SNA in control rats. This response was significantly attenuated in rats given access to dexamethasone for 7, but not 1, days. Similarly, injection of insulin into the lateral ventricle or locally within the ARC significantly increased lumbar SNA in control rats but this response was absent in rats given access to dexamethasone. The lack of a sympathetic response to insulin cannot be attributed to a generalized depression of sympathetic function or inactivation of ARC neurons as electrical activation of sciatic afferents or ARC injection of gabazine, respectively, produced similar increases in SNA between control and dexamethasone-treated rats. Western blot analysis indicates insulin produced similar activation of Akt Ser(473) and rpS6(S240/244) in the ventromedial hypothalamus of control and dexamethasone-treated rats. Collectively, these findings suggest that dexamethasone attenuates the sympathoexcitatory actions of insulin through a disruption of ARC neuronal function downstream of Akt or mTOR signaling.
    Journal of Neurophysiology 09/2014; DOI:10.1152/jn.00514.2014 · 3.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cerebrospinal fluid (CSF) provides an invaluable analytical window to the central nervous system (CNS) because it reflects the dynamically changing complement of CNS constituents. We describe an improved method for sampling CSF in rats that is easy to perform. It has a 96% success rate of CSF collection and consistently yields large volumes (150-200 μl) of CSF. The blood contamination rate is also low (6%) as determined by both visual inspection and the lack of molecular detection of apolipoprotein B, a plasma-derived protein, which is absent in the CNS. This improved method of CSF sampling can have broad applicability in physiological and pharmacological evaluation for diverse CNS targets. We used this technique to provide proof of principle by examining the effect of intraperitoneal insulin on the level of apolipoprotein E (apoE) in the CSF. Insulin (0.5 and 1 U/kg) led to a significant increase of insulin in both plasma and CSF at 2 h after intraperitoneal administration and decreased blood glucose for at least 2h. ApoE concentrations in CSF, but not in plasma, were also significantly increased, and its time-course was inversely correlated with the alterations in blood glucose over 2 h. These results provide a pharmacological validation of the novel CSF sampling and validation procedure for sampling rat CSF.
    Journal of neuroscience methods 06/2012; 209(1):106-12. DOI:10.1016/j.jneumeth.2012.05.034 · 1.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have demonstrated the satiating properties of soups compared with solids; however, the mechanisms controlling soup-induced satiety are unknown. This study aimed to understand the physiological mechanisms causing soup to be more satiating. A total of 12 volunteers were tested on three occasions after a solid meal, chunky soup or smooth soup test meal for gastric emptying (GE) using the sodium [1-(13)C] acetate breath test, satiety using visual analog scales (VAS) and glycaemic response (GR) using finger prick blood samples. There was a significant difference in GE half-time (P=0.022) and GE ascension time (P=0.018), with the longest GE times for the smooth soup and the shortest for the solid meal. The GR area under the curve was significantly different between meals (P=0.040). The smooth soup had the greatest GR (87.0±49.5 mmol/l/min), followed by the chunky soup (65.4±48.0 mmol/l/min), with the solid meal having the lowest GR (61.6±36.8 mmol/l/min). Volunteers were fuller after the smooth soup compared with solid meal (P=0.034). The smooth soup induced greater fullness compared with the solid meal because of a combination of delayed GE leading to feelings of gastric distension and rapid accessibility of nutrients causing a greater glycaemic response.European Journal of Clinical Nutrition advance online publication, 24 October 2012; doi:10.1038/ejcn.2012.152.
    European journal of clinical nutrition 10/2012; DOI:10.1038/ejcn.2012.152 · 2.95 Impact Factor