Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Diabetes Obes Metab ; 16 Suppl 1: 26-32, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25200293

ABSTRACT

It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases.


Subject(s)
Brain/metabolism , Feedback, Physiological , Glucokinase/metabolism , Glucose/metabolism , Islets of Langerhans/metabolism , Models, Neurological , Neurons/metabolism , Animals , Brain/cytology , Diabetes Mellitus/metabolism , Energy Metabolism , Glucokinase/genetics , Humans , Hypoglycemia/metabolism , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/innervation , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neuroglia/cytology , Neuroglia/metabolism , Neurons/cytology , Obesity/metabolism , Organ Specificity
2.
Diabetologia ; 55(11): 3094-103, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22872212

ABSTRACT

AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) is an enteroendocrine hormone that promotes storage of glucose and fat. Its secretion from intestinal K cells is triggered by nutrient ingestion and is modulated by intracellular cAMP. In view of the proadipogenic actions of GIP, this study aimed to identify pathways in K cells that lower cAMP levels and GIP secretion. METHODS: Murine K cells purified by flow cytometry were analysed for expression of G(αi)-coupled receptors by transcriptomic microarrays. Somatostatin and cannabinoid receptor expression was confirmed by quantitative RT-PCR. Hormone secretion in vitro was measured in GLUTag and primary murine intestinal cultures. cAMP was monitored in GLUTag cells using the genetically encoded sensor Epac2-camps. In vivo tolerance tests were performed in cannulated rats. RESULTS: Purified murine K cells expressed high mRNA levels for somatostatin receptors (Sstrs) Sstr2, Sstr3 and Sstr5, and cannabinoid receptor type 1 (Cnr1, CB1). Somatostatin inhibited GIP and glucagon-like peptide-1 (GLP-1) secretion from primary small intestinal cultures, in part through SSTR5, and reduced cAMP generation in GLUTag cells. Although the CB1 agonist methanandamide (mAEA) inhibited GIP secretion, no significant effect was observed on GLP-1 secretion from primary cultures. In cannulated rats, treatment with mAEA prior to an oral glucose tolerance test suppressed plasma GIP but not GLP-1 levels, whereas the CB1 antagonist AM251 elevated basal GIP concentrations. CONCLUSIONS/INTERPRETATION: GIP release is inhibited by somatostatin and CB1 agonists. The differential effects of CB1 ligands on GIP and GLP-1 release may provide a new tool to dissociate secretion of these incretin hormones and lower GIP but not GLP-1 levels in vivo.


Subject(s)
Colon/metabolism , Gastric Inhibitory Polypeptide/metabolism , Intestine, Small/metabolism , Receptor, Cannabinoid, CB1/metabolism , Receptors, Somatostatin/metabolism , Animals , Colon/cytology , Cyclic AMP/metabolism , Enteroendocrine Cells/cytology , Enteroendocrine Cells/metabolism , Glucagon-Like Peptide 1/metabolism , Incretins/metabolism , Intestine, Small/cytology , Male , Mice , Mice, Inbred C57BL , Primary Cell Culture , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Cannabinoid, CB1/genetics , Receptors, Somatostatin/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...