Central infusion of glucagon-like peptide-1-(7–36) amide (GLP-1) receptor antagonist attenuates lithium chloride-induced c-Fos induction in rat brainstem

Thiele, T.E.; Seeley, Randy J.; D’Alessio, David A.; Eng, John; Bernstein, Ilene L.; Woods, Stephen C.; Dijk, van Jitse

doi:10.1016/s0006-8993(98)00584-8

Cited by 80 publications

(61 citation statements)

References 22 publications

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“…Our results also provide a potential molecular mechanism for the similar effect of lithium and GLP-1 to suppress food and water intake (3,4,(63)(64)(65)(66)(67)(68)(69)(70). Scientists have observed for a number of years that peripheral administration of lithium in rats causes a spectrum of effects, including reduced food/water intake, decreased salt ingestion after sodium depletion, and induced robust conditioned taste aversions (63)(64)(65)(66)(67)(68)(69).…”

Section: Discussionmentioning

confidence: 69%

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

Ni¹,

Anini²,

Fang³

et al. 2003

Journal of Biological Chemistry

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The proglucagon gene encodes several peptide hormones that regulate blood glucose homeostasis, growth of the small intestine, and satiety. Among them, glucagon-like peptide 1 (GLP-1) lowers blood glucose levels in patients with diabetes and inhibits eating and drinking in fasted rats. Although proglucagon transcription and GLP-1 synthesis were shown to be activated by forskolin and other protein kinase A (PKA) activators, deleting or mutating the cAMP-response element (CRE) only moderately attenuates the proglucagon gene promoter in response to PKA activation. Therefore, PKA may activate proglucagon transcription via a mechanism independent of the CRE motif. Recently, PKA was shown to phosphorylate and inactivate GSK-3␤, a key mediator in the Wnt signaling pathway. We show here that lithium, an inhibitor of GSK-3␤, activates proglucagon gene transcription and stimulates GLP-1 synthesis in an intestinal endocrine L cell line, GLUTag. The activation was also observed in primary fetal rat intestinal cell (FRIC) cultures, but not in a pancreatic A cell line. Co-transfection of ␤-catenin, a downstream effector of GSK-3␤ activities, activated the proglucagon gene promoter without a CRE. Furthermore, forskolin and 8-Br-cAMP phosphorylated GSK-3␤ at serine 9 in intestinal proglucagon-producing cells, and both lithium and forskolin induced the accumulation of free ␤-catenin in these cell lines. These observations indicate that the proglucagon gene is among the targets of the Wnt signaling pathway.

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Section: Discussionmentioning

confidence: 69%

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

Ni¹,

Anini²,

Fang³

et al. 2003

Journal of Biological Chemistry

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“…Future studies will be required to determine which Wnt molecule(s) regulates glu gene expression in the gut endocrine cells and whether glu expression in the brain is also regulated by lithium and the Wnt pathway. Peripheral administration of lithium was found to reduce food/water intake, decrease salt ingestion after sodium depletion, and induce robust conditioned taste aversion in rats (42)(43)(44)(45)(46)(47)(48)(49). These effects can be mimicked by central (intracerebroventricular) administration of GLP-1 (14).…”

Section: Discussionmentioning

confidence: 99%

TCF-4 Mediates Cell Type-specific Regulation of Proglucagon Gene Expression by β-Catenin and Glycogen Synthase Kinase-3β

Brubaker

Jin

2005

Journal of Biological Chemistry

391

329

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The proglucagon gene (glu) encodes glucagon, expressed in pancreatic islets, and the insulinotropic hormone GLP-1, expressed in the intestines. These two hormones exert critical and opposite effects on blood glucose homeostasis. An intriguing question that remains to be answered is whether and how glu gene expression is regulated in a cell type-specific manner. We reported previously that the glu gene promoter in gut endocrine cell lines was stimulated by ␤-catenin, the major effector of the Wnt signaling pathway, whereas glu mRNA expression and GLP-1 synthesis were activated via inhibition of glycogen synthase kinase-3␤, the major negative modulator of the Wnt pathway (Ni, Z

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“…More importantly, pretreatment with the GLP-1 receptor antagonist also attenuated LiCl-induced c-FLI in the AP, NTS, and PBN. 62 We later found that the GLP-1 antagonist did not influence cholecystokinin octapeptide (CCK-8) induced c-FLI, indicating that the compound does not block c-FLI indiscriminately (unpublished data), nor did this antagonist block i3vt CCK-8's ability to produce a short-term reduction in food intake. These data indicate that central blockade of the GLP-1 receptor attenuates LiCl-induced cFLI, and suggest that neuronal activity in the brainstem caused by LiCl administration is mediated, at least in part, by GLP-1 signaling.…”

Section: Involvement Of Glp-1 Signaling In Licl-induced Neuronal Actimentioning

confidence: 98%

“…) may be involved with neuronal signaling in the brainstem following injection of LiCl. 62 A hint of such a mechanism has been provided by Rinaman,63 who observed that peripheral administration of toxins, including LiCl, stimulated c-FLI in neuronal cell bodies in the NTS that contain GLP-1. Combined tracer injections indicated that a portion of these project to the PVN.…”

Section: Involvement Of Glp-1 Signaling In Licl-induced Neuronal Actimentioning

confidence: 99%

Glucagon-like peptide-1 (7–36) amide: a central regulator of satiety and interoceptive stress

Dijk

Thiele

1999

Neuropeptides

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INTRODUCTIONIngestion of food is a necessary and pleasant occupation that allows humans and other species to maintain caloric homeostasis and a certain level of body weight. Ironically, in doing so, one's 'milieu interieur' is put at risk because meal-induced fuel excursions can have deleterious effects on metabolic (e.g. glycosylation causing loss of enzymatic efficacy) and cardiovascular (e.g. triglyceride accumulation, increased blood pressure, etc.) processes. 1,2 To reduce these perturbations to a minimum, evolution has provided many species (including humans and rodents) with a fine-tuned system enabling ingested nutrients to be anticipated, efficiently digested, and stored. 3 One of these mechanisms includes passage of nutrients through the digestive tract, triggering the release of a number of peptides from endocrine cells located in the wall of various parts of the gastrointestinal tract. These peptides serve important functions in facilitating the process of nutrient digestion/storage. Among these, the truncated (i.e. 7-36) amidated form of glucagon-like peptide-1 (GLP-1) has attracted considerable attention over the last several years. Firstly, because of its remarkable peripheral insulinotropic effects that could be useful for clinical purposes. Secondly, because more recent data suggest an important role of this peptide in the central nervous system (CNS) control of ingestive behavior. Although the present paper mainly focusses on the latter issue, a short review of peripheral GLP mechanisms is necessary for a better understanding of the processes that relate GLP-1 to food intake. GLP-1 FROM THE GASTROINTESTINAL TRACTGLP-1 is processed from proglucagon in mucosal L cells of the distal portion of the ileum and in the A cells of the pancreas. Ingested food, particularly when rich in carbohydrates, causes the level of circulating GLP-1 (mainly of ileal origin) to increase, and in turn, GLP-1 potently stimulates the secretion of insulin from pancreatic B cells via receptor-mediated processes (for reviews, see refs 4 and 5). In contrast, it reduces the secretion of glucagon, at least under ad libitum feeding conditions. 6 While GLP-1 may have some direct stimulatory effects on glucose clearance in peripheral tissue 7,8 (presumably via activation of specific GLP-1 receptors in liver, muscle, kidney Summary Glucagon-like peptide-1 (7-36) amide (GLP-1) is processed from proglucagon in the distal ileum as well as in the CNS. In the periphery, GLP-1 acts as an incretin factor and profoundly inhibits upper gastrointestinal motility ('ileal brake'), the latter presumably involving the CNS. Within the CNS, GLP-1 has a satiating effect, since administration of GLP-1 into the third cerebral ventricle reduces short-term food intake (and meal size), while administration of GLP-1 antagonists have the opposite effect. In addition, activation of GLP-1 receptors in certain brain regions elicits strong taste aversions. Similarities between toxin-and GLP-1-induced neuronal activity in the CNS (brain stem) suggest a role f...

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Central infusion of glucagon-like peptide-1-(7–36) amide (GLP-1) receptor antagonist attenuates lithium chloride-induced c-Fos induction in rat brainstem

Cited by 80 publications

References 22 publications

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

TCF-4 Mediates Cell Type-specific Regulation of Proglucagon Gene Expression by β-Catenin and Glycogen Synthase Kinase-3β

Glucagon-like peptide-1 (7–36) amide: a central regulator of satiety and interoceptive stress

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