ABSTRACT. Objective. The prevalence of obesity has increased dramatically in recent years. However, the role of dietary composition in body weight regulation remains unclear. The purpose of this work was to investigate the acute effects of dietary glycemic index (GI) on energy metabolism and voluntary food intake in obese subjects.Methods. Twelve obese teenage boys were evaluated on three separate occasions using a crossover study protocol. During each evaluation, subjects consumed identical test meals at breakfast and lunch that had a low, medium, or high GI. The high-and medium-GI meals were designed to have similar macronutrient composition, fiber content, and palatability, and all meals for each subject had equal energy content. After breakfast, plasma and serum concentrations of metabolic fuels and hormones were measured. Ad libitum food intake was determined in the 5-hour period after lunch.Results. Voluntary energy intake after the high-GI meal (5.8 megajoule [mJ]) was 53% greater than after the medium-GI meal (3.8 mJ), and 81% greater than after the low-GI meal (3.2 mJ). In addition, compared with the low-GI meal, the high-GI meal resulted in higher serum insulin levels, lower plasma glucagon levels, lower postabsorptive plasma glucose and serum fatty acids levels, and elevation in plasma epinephrine. The area under the glycemic response curve for each test meal accounted for 53% of the variance in food intake within subjects.Conclusions. The rapid absorption of glucose after consumption of high-GI meals induces a sequence of hormonal and metabolic changes that promote excessive food intake in obese subjects. Additional studies are needed to examine the relationship between dietary GI and long-term body weight regulation. American Heart Association, 7 and American Diabetes Association 8 currently advocate consumption of a low-fat diet in the prevention and treatment of obesity. Recently, however, the relationship between dietary fat and obesity has been questioned on several grounds 9 -11 including that both cross-sectional and longitudinal analyses have failed to show a consistent association between dietary fat and body fat, 10,12,13 and that weight loss on low-fat diets is usually modest and transient. 9,14 In addition, and perhaps of particular significance, mean fat intake in the United States reportedly has decreased over the past 3 decades, from 42% to ϳ34% of dietary energy, 11,12,15,16 whereas the rate of obesity has continued to rise.Another dietary factor that may influence body weight is the glycemic index (GI). GI a is a property of carbohydrate-containing food that describes the rise of blood glucose occurring after a meal. 17 Foods that are rapidly digested and absorbed or transformed metabolically into glucose have a high GI. 18 -22 The GI of a meal is determined primarily by the amount of carbohydrate consumed and by other dietary factors affecting food digestibility, gastrointestinal motility, or insulin secretion (including carbohydrate type, food structure, fiber, protein, and fat). ...

Histamine H 3 receptors modulate histamine synthesis, although little is known about the transduction mechanisms involved. To investigate this issue, we have used a preparation of rat brain cortical miniprisms in which histamine synthesis can be modulated by depolarization and by H 3 receptor ligands. When the miniprisms were incubated in presence of forskolin, dibutyryl-cAMP, or 3-isobutyl-1-methylxanthine (IBMX), histamine synthesis was stimulated in 34, 29, and 47%, respectively. These stimulations could be prevented by the selective cAMP protein kinase blocker Rp-adenosine 3Ј,5Ј-cyclic monophosphothioate triethylamine (Rp-cAMPs). Preincubation with the H 3 receptor agonist imetit prevented IBMX-(100% blockade) and forskolin-(70% blockade) induced stimulation of histamine synthesis. The H 3 inverse agonist thioperamide enhanced histamine synthesis in the presence of 1 mM IBMX or 30 mM potassium (ϩ47 and ϩ45%, respectively). Similarly, the H 3 antagonist clobenpropit enhanced histamine synthesis in the presence of 30 mM potassium (ϩ 59%). The cAMP-dependent protein kinase blockers Rp-cAMPs and PKI14 -22 could impair the effects of thioperamide and clobenpropit, respectively. These results indicate that the adenylate cyclase-protein kinase A pathway is involved in the modulation of histamine synthesis by H 3 autoreceptors present in histaminergic nerve terminals.

Abstract:The properties and regulation of the polyamine transport system in brain are still poorly understood. The present study shows, for the first time, the existence of a polyamine transport system in cerebellar astrocytes and suggests that polyamine uptake is mediated by a single and saturable high-affinity transport system for putrescine, spermine, and spermidine (K m ϭ 3.2, 1.2, and 1.8 M, respectively). Although substitution of NaCl by choline chloride produced a decrease in the putrescine, spermine, and spermidine uptake, it seems that polyamine transport in cerebellar astrocytes is not mediated by an Na ϩ cotransport as in the presence of Na ϩ and cholinium, polyamine uptake was much lower than when measured in a sucrose-based medium. On the other hand, ouabain, gramicidin (a Na ϩ ionophore), and ionomycin (a Ca 2ϩ ionophore) produced a strong inhibition of polyamine uptake, suggesting that membrane potential could have an important role in the functioning of the astroglial polyamine uptake system. Moreover, protein kinase C inhibition produced an enhancement of polyamine uptake, whereas stimulation of protein kinase C with phorbol esters inhibited polyamine uptake. Alternatively, the tyrosine kinase inhibitor genistein caused a marked reduction in the uptake. No effects on polyamine uptake were observed with inhibitors and activators of cyclic AMP-dependent protein kinase or when Ca 2ϩ /calmodulin-dependent protein kinase II was inhibited with KN-62. These results suggest that the polyamine uptake system in cerebellar astrocytes could be modulated by protein kinase C and tyrosine kinase activities. Key Words: Uptake-Polyamines-Astrocytes-Protein kinases-Spermine-Spermidine-Putrescine. J. Neurochem. 75, 1917Neurochem. 75, -1926Neurochem. 75, (2000.Spermine, spermidine, and putrescine are ubiquitous polyamines that are synthesized from ornithine in a pathway that is controlled mainly by the rate of ornithine decarboxylase activity (Tabor and Tabor, 1984;Pegg and McCann, 1988). In the CNS, polyamines have been associated with normal growth and differentiation, and the changes in ornithine decarboxylase activity appear to closely follow the region-specific pattern of cell proliferation (Slotkin and Bartolome, 1986). Furthermore, polyamines have been reported to play a significant role in nerve growth and nerve regeneration (Ingoglia et al., 1982;Gilad and Gilad, 1983).In addition, intracellular polyamines have been described to have other roles in the CNS as second messengers (Koenig et al., 1983;Iqbal and Koenig, 1985) or as modulators of neuronal ion channels (Bowie and Mayer, 1995;Donevan and Ragawski, 1995). In particular, activity-dependent relief of the blocking effect of polyamines on ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors has been recently suggested to contribute to short-term plasticity in local cortical circuits (Rozov and Burnashev, 1999).Brain polyamines like putrescine, spermine, and spermidine can be released, in a Ca 2ϩ -dependent manner, by depolarizing co...

H 3 autoreceptors provide feedback control of neurotransmitter synthesis in histaminergic neurons, but the transduction pathways involved are poorly understood. In rat brain cortical slices, histamine synthesis can be stimulated by depolarization and inhibited by H 3 agonists. We show that histamine synthesis stimulation by depolarization with 30 mM K ϩ requires extracellular calcium entry, mostly through N-type channels, and subsequent activation of calcium/calmodulin-dependent protein kinase type II. In vitro, this kinase phosphorylated and activated histidine decarboxylase, the histamine-synthesizing enzyme. Inhibition of depolarization-stimulated histamine synthesis by the histamine H 3 receptor agonist imetit was impaired by preincubation with pertussis toxin and by the presence of a myristoylated peptide (myristoyl-N-QEHAQEPERQYMHIGTMVE-FAYALVGK) blocking the actions of G-protein ␤␥ subunits. The stimulation of another G i/o -coupled receptor, adenosine A 1 , also decreased depolarization-stimulated histamine synthesis. In contrast, protein kinase A activation, which is also repressed by H 3 receptors, elicited a depolarization-and calcium/calmodulin-independent stimulation of histamine synthesis. Protein kinase A was able also to phosphorylate and activate histidine decarboxylase in vitro. These results show how depolarization activates histamine synthesis in nerve endings and demonstrate that both pathways modulating neurotransmitter synthesis are controlled by H 3 autoreceptors.