GLP-1 (7 - 36) Amide: Effects on Glucose Transport and Metabolism in Rat Adipose Tissue

Perea, A.; Viñambres, Concepción; Clemente, Felipe; Villanueva-Peñacarrillo, María Luisa; Valverde, Isabel

doi:10.1055/s-2007-979068

Cited by 45 publications

(29 citation statements)

References 3 publications

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“…At this submaximal concentration, the combined effect of both peptides on both glycogen synthesis and glycogen synthase a activity was additive, whereas at 10 10 mol/l no further increment was detected, indicating that GLP-1 may share the insulinsignaling pathway at some post-receptor level. These in vitro effects were previously observed in skeletal muscle from normal ) and diabetic (Morales et al 1997) rats, mice (O'Harte et al 1997), and also in the rat myocyte cell line L6 (Yang et al 1998), rat adipocytes (Oben et al 1991, Miki et al 1996, Perea et al 1997) and mice adipocyte cell line 3T3-L1 . The activating action of GLP-1 on glycogen synthesis and synthase a activity in human myotubes was maintained after 48 h exposure to the peptide, which supports the long-term therapeutic value of GLP-1.…”

Section: Discussionsupporting

confidence: 61%

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Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes

Luque¹,

González²,

Márquez³

et al. 2002

Journal of Endocrinology

117

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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 doserelated increase of the -[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.

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Section: Discussionsupporting

confidence: 61%

“…In the adipose tissue of the rat, it was observed that GLP-1 not only exerts an action on lipid metabolismdose-dependently lipolytic and/or lipogenic (Ruiz-Gande et al 1992, Perea et al 1997) -but also, as in liver and muscle, that it stimulates parameters involved in glucose metabolism (Perea et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes

Luque¹,

González²,

Márquez³

et al. 2002

Journal of Endocrinology

117

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“…It has been shown that GLP-1, at physiological concentrations, directly stimulates glycogen synthesis in rat skeletal muscle (44) and rat adipose tissue (45), which is accompanied by an increase in glycogen synthase-a activity (44), which will lower plasma glucose levels. Glycogen synthase-a activity is also increased in hepatocytes from normal and diabetic rats (46).…”

Section: Extrapancreatic Effectsmentioning

confidence: 99%

Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function

Perfetti

Merkel

2000

European Journal of Endocrinology

126

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Glucagon-like peptide-1 (GLP-1) is a gut hormone synthesized by post-translational processing in intestinal L-cells, and it is released in response to food ingestion. GLP-1 stimulates insulin secretion during hyperglycemia, suppresses glucagon secretion, stimulates (pro)-insulin biosynthesis and decreases the rate of gastric emptying and acid secretion. GLP-1 has also been shown to have a prosatiety effect. In addition, it has been demonstrated that a long-term infusion with GLP-1, or exendin-4, a long-acting analog of human GLP-1, increases b-cell mass in rats. In conclusion, GLP-1 appears to regulate plasma glucose levels via various and independent mechanisms. GLP-1 is an excellent candidate option for the treatment of patients with type 2 diabetes mellitus.

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“…Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide that has been proposed as a possible tool for the therapy of type 2 diabetes (Gutniak et al 1992); it has incretin character and insulin-independent antidiabetic properties (Gutniak et al 1992, D'Alessio et al 1995, and mimics the effects of insulin on glucose metabolism in the skeletal muscle and liver from normal ) and diabetic rats (Morales et al 1997), and also in fat (Perea et al 1997, Villanueva-Peñacarrillo et al 2001a. In these extrapancreatic tissues, GLP-1 seems to act through specific receptors (Mérida et al 1993, Valverde et al 1993, Delgado et al 1995, Villanueva-Peñacarrillo et al 1995a,b, Yang et al 1998 which, unlike the pancreatic one (Thorens 1992), are not associated with an activation of adenylate cyclase , Yang et al 1998.…”

Section: Introductionmentioning

confidence: 99%

Cell signalling of glucagon-like peptide-1 action in rat skeletal muscle

Acitores

González²,

Sancho³

et al. 2004

Journal of Endocrinology

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Glucagon-like peptide-1 (GLP-1), an incretin with glucose-dependent insulinotropic and insulinindependent antidiabetic properties, has insulin-like effects on glucose metabolism in extrapancreatic tissues participating in overall glucose homeostasis. These effects are exerted through specific receptors not associated with cAMP, an inositol phosphoglycan being a possible second messenger. In rat hepatocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB), protein kinase C (PKC) and protein phosphatase 1 (PP-1) has been shown to be involved in the GLP-1-induced stimulation of glycogen synthase. We have investigated the role of enzymes known or suggested to mediate the actions of insulin in the GLP-1-induced increase in glycogen synthase a activity in rat skeletal muscle strips.We first explored the effect of GLP-1, compared with that of insulin, on the activation of PI3K, PKB, p70s6 kinase (p70s6k) and p44/42 mitogen-activated protein kinases (MAPKs) and the action of specific inhibitors of these kinases on the insulin-and GLP-1-induced increment in glycogen synthase a activity.The study showed that GLP-1, like insulin, activated PI3K/PKB, p70s6k and p44/42. Wortmannin (a PI3K inhibitor) reduced the stimulatory action of insulin on glycogen synthase a activity and blocked that of GLP-1, rapamycin (a 70s6k inhibitor) did not affect the action of GLP-1 but abolished that of insulin, PD98059 (MAPK inhibitor) was ineffective on insulin but blocked the action of GLP-1, okadaic acid (a PP-2A inhibitor) and tumour necrosis factor-(a PP-1 inhibitor) were both ineffective on GLP-1 but abolished the action of insulin, and Ro 31-8220 (an inhibitor of some PKC isoforms) reduced the effect of GLP-1 while completely preventing that of insulin.It was concluded that activation of PI3K/PKB and MAPKs is required for the GLP-1-induced increment in glycogen synthase a activity, while PKC, although apparently participating, does not seem to play an essential role; unlike in insulin signaling, p70s6k, PP-1 and PP-2A do not seem to be needed in the action of GLP-1 upon glycogen synthase a activity in rat muscle.

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GLP-1 (7 - 36) Amide: Effects on Glucose Transport and Metabolism in Rat Adipose Tissue

Cited by 45 publications

References 3 publications

Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes

Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes

Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function

Cell signalling of glucagon-like peptide-1 action in rat skeletal muscle

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