Search Results
Search for other papers by G Üçkaya in
Google Scholar
PubMed
Search for other papers by P Delagrange in
Google Scholar
PubMed
Search for other papers by A Chavanieu in
Google Scholar
PubMed
Search for other papers by G Grassy in
Google Scholar
PubMed
Search for other papers by M-F Berthault in
Google Scholar
PubMed
Search for other papers by A Ktorza in
Google Scholar
PubMed
Search for other papers by E Cerasi in
Google Scholar
PubMed
Search for other papers by G Leibowitz in
Google Scholar
PubMed
Search for other papers by N Kaiser in
Google Scholar
PubMed
that aim to improve β-cell function and survival. Glucagon-like peptide 1 (GLP-1) is a potent incretin hormone secreted by the intestinal L cells in response to food intake ( Drucker 2001 ). GLP-1 exerts multiple effects on pancreatic β
Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK
Search for other papers by K K Sidhu in
Google Scholar
PubMed
Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK
Search for other papers by R C Fowkes in
Google Scholar
PubMed
Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK
Search for other papers by R H Skelly in
Google Scholar
PubMed
Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK
Search for other papers by J M Burrin in
Google Scholar
PubMed
Introduction Glucagon-like peptide 1 (GLP-1) is a proglucagon-derived peptide hormone that is synthesized and secreted by intestinal L-cells in response to the ingestion of nutrients and circulates to the pancreas where it stimulates
Department of Vascular Biology, GlaxoSmithKline Pharmaceuticals, Third Avenue, Harlow, CM19 5AW, UK
Search for other papers by Colin W Hay in
Google Scholar
PubMed
Department of Vascular Biology, GlaxoSmithKline Pharmaceuticals, Third Avenue, Harlow, CM19 5AW, UK
Search for other papers by Elaine M Sinclair in
Google Scholar
PubMed
Department of Vascular Biology, GlaxoSmithKline Pharmaceuticals, Third Avenue, Harlow, CM19 5AW, UK
Search for other papers by Giovanna Bermano in
Google Scholar
PubMed
Department of Vascular Biology, GlaxoSmithKline Pharmaceuticals, Third Avenue, Harlow, CM19 5AW, UK
Search for other papers by Elaine Durward in
Google Scholar
PubMed
Department of Vascular Biology, GlaxoSmithKline Pharmaceuticals, Third Avenue, Harlow, CM19 5AW, UK
Search for other papers by Mohammad Tadayyon in
Google Scholar
PubMed
Department of Vascular Biology, GlaxoSmithKline Pharmaceuticals, Third Avenue, Harlow, CM19 5AW, UK
Search for other papers by Kevin Docherty in
Google Scholar
PubMed
Introduction Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the enteroendocrine L-cells of the small intestine in response to food intake ( Kieffer & Habener 1999 , Drucker 2001 ). GLP-1 plays an important role in
Search for other papers by Patricia Vázquez in
Google Scholar
PubMed
Search for other papers by Isabel Roncero in
Google Scholar
PubMed
Search for other papers by Enrique Blázquez in
Google Scholar
PubMed
Search for other papers by Elvira Alvarez in
Google Scholar
PubMed
facilitate the action of these proteins involved in the signalling process ( Pawson & Scott 1997 ). The glucagon-like peptide-1 (GLP-1) receptor is a member of the G-protein-coupled receptor subfamily ( Dillon et al. 1993 , Thorens 1993 , Thorens
Search for other papers by M L Villanueva-Peñacarrillo in
Google Scholar
PubMed
Search for other papers by E Delgado in
Google Scholar
PubMed
Search for other papers by M A Trapote in
Google Scholar
PubMed
Search for other papers by A Alcántara in
Google Scholar
PubMed
Search for other papers by F Clemente in
Google Scholar
PubMed
Search for other papers by M A Luque in
Google Scholar
PubMed
Search for other papers by A Perea in
Google Scholar
PubMed
Search for other papers by I Valverde in
Google Scholar
PubMed
Abstract
We have found [125I]glucagon-like peptide (GLP)-1(7–36)amide specific binding activity in rat liver and isolated hepatocyte plasma membranes, with an Mr of approximately 63 000, estimated by cross-linking and SDS-PAGE. The specific binding was time- and membrane protein concentration-dependent, and equally displaced by unlabelled GLP-1(7–36)amide and by GLP-1(1–36)amide, achieving its ID50 at 3×10−9 m of the peptides. GLP-1(7–36)amide did not modify the basal or the glucagon (10−8 m)-stimulated adenylate cyclase in the hepatocyte plasma membranes. These data, together with our previous findings of a potent glycogenic effect of GLP-1(7–36)amide in isolated rat hepatocytes, led us to postulate that the insulin-like effects of this peptide on glucose liver metabolism could be mediated by a type of receptor probably different from that described for GLP-1 in pancreatic B-cells or, alternatively, by the same receptor which, in this tissue as well as in muscle, uses a different transduction system.
Journal of Endocrinology (1995) 146, 183–189
Search for other papers by Raylene A Reimer in
Google Scholar
PubMed
Introduction Glucagon-like peptide-1 (GLP-1) is a gut hormone released from intestinal L-cells in response to food ingestion ( Kieffer & Habener 1999 ). In addition to potentiating glucose-dependent insulin secretion, GLP-1
Search for other papers by C Herrmann-Rinke in
Google Scholar
PubMed
Search for other papers by A Vöge in
Google Scholar
PubMed
Search for other papers by M Hess in
Google Scholar
PubMed
Search for other papers by B Göke in
Google Scholar
PubMed
Abstract
Food ingestion induces a rapid increase in the insulinotropic glucagon-like peptide-1 (GLP-1) in plasma. Paradoxically, GLP-1 originates from the lower intestines and therefore a complex regulation of postprandial GLP-1 secretion must exist. This was addressed in the present study by utilizing an isolated vascularly perfused rat ileum preparation. Peptides and neurotransmitters thought to be candidate mediators triggering GLP-1 secretion were arterially infused and GLP-1 was measured in the venous effluent. Arterial infusion of cholinergic agonists strongly enhanced GLP-1 secretion which was counteracted by the addition of atropine. Histamine, dopamine, 5-hydoxytryptamine, γ-aminobutyric acid, and norepinephrine had no effect. Peptides of the bombesin family were strong stimulants whereas tachykinins, enkephalins, dynorphin, TRH, calcitonin-gene-related peptide and members of the secretin family, vasoactive intestinal peptide, peptide histidine isoleucine and neuropeptide Y, were less effective. The second incretin hormone, gastric inhibitory polypeptide (GIP), was the most potent stimulant of GLP-1 secretion in our study. It enhanced GLP-1 release up to sixfold above basal during the early phase followed by a sustained secretion at 400% above basal. This stimulation remained unaffected by atropine. In conclusion, in addition to luminal stimulation of nutrients, a cholinergic impulse as well as peptidergic mediators (among them possibly GIP and GRP) may have an impact on postprandial GLP-1 secretion from the rat ileum.
Journal of Endocrinology (1995) 147, 25–31
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by J C Parker in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by K S Lavery in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by N Irwin in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by B D Green in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by B Greer in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by P Harriott in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by F P M O’Harte in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by V A Gault in
Google Scholar
PubMed
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
Search for other papers by P R Flatt in
Google Scholar
PubMed
Introduction Glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important gastrointestinal-releasing hormones involved in the regulation of postprandial nutrient homeostasis ( Meier et al
Search for other papers by MA Luque in
Google Scholar
PubMed
Search for other papers by N Gonzalez in
Google Scholar
PubMed
Search for other papers by L Marquez in
Google Scholar
PubMed
Search for other papers by A Acitores in
Google Scholar
PubMed
Search for other papers by A Redondo in
Google Scholar
PubMed
Search for other papers by M Morales in
Google Scholar
PubMed
Search for other papers by I Valverde in
Google Scholar
PubMed
Search for other papers by ML Villanueva-Penacarrillo in
Google Scholar
PubMed
Glucagon-like peptide-1 (GLP-1) has been shown to have insulin-like effects upon the metabolism of glucose in rat liver, muscle and fat, and on that of lipids in rat and human adipocytes. These actions seem to be exerted through specific receptors which, unlike that of the pancreas, are not - at least in liver and muscle - cAMP-associated. Here we have investigated the effect, its characteristics, and possible second messengers of GLP-1 on the glucose metabolism of human skeletal muscle, in tissue strips and primary cultured myocytes. In muscle strips, GLP-1, like insulin, stimulated glycogen synthesis, glycogen synthase a activity, and glucose oxidation and utilization, and inhibited glycogen phosphorylase a activity, all of this at physiological concentrations of the peptide. In cultured myotubes, GLP-1 exerted, from 10(-13) mol/l, a dose-related increase of the D-[U-(14)C]glucose incorporation into glycogen, with the same potency as insulin, together with an activation of glycogen synthase a; the effect of 10(-11) mol/l GLP-1 on both parameters was additive to that induced by the equimolar amount of insulin. Synthase a was still activated in cells after 2 days of exposure to GLP-1, as compared with myotubes maintained in the absence of peptide. In human muscle cells, exendin-4 and its truncated form 9-39 amide (Ex-9) are both agonists of the GLP-1 effect on glycogen synthesis and synthase a activity; but while neither GLP-1 nor exendin-4 affected the cellular cAMP content after 5-min incubation in the absence of 3-isobutyl-1-methylxantine (IBMX), an increase was detected with Ex-9. GLP-1, exendin-4, Ex-9 and insulin all induced the prompt hydrolysis of glycosylphosphatidylinositols (GPIs). This work shows a potent stimulatory effect of GLP-1 on the glucose metabolism of human skeletal muscle, and supports the long-term therapeutic value of the peptide. Further evidence for a GLP-1 receptor in this tissue, different from that of the pancreas, is also illustrated, suggesting a role for an inositolphosphoglycan (IPG) as at least one of the possible second messengers of the GLP-1 action in human muscle.
Search for other papers by L Friis-Hansen in
Google Scholar
PubMed
Search for other papers by KA Lacourse in
Google Scholar
PubMed
Search for other papers by LC Samuelson in
Google Scholar
PubMed
Search for other papers by JJ Holst in
Google Scholar
PubMed
The maturation of many peptide hormones is attenuated in carboxypeptidase E (CPE)-deficient fat/fat mice, leading to a slowly developing, adult-onset obesity with mild diabetes. To determine the contribution of the hormones generated from the proglucagon precursor to this phenotype, we studied the tissue-specific processing of glucagon and glucagon-like peptide-1 (GLP-1) in these mice. In all tissues examined there was a great reduction in mature amidated GLP-1. Furthermore, a lack of CPE attenuates prohormone convertase processing of proglucagon in both the pancreas and the intestine. These findings suggest that defects in proglucagon processing together with other endocrine malfunctions could contribute to the diabetic and obesity phenotype in fat/fat mice.
