Glucagon-like peptide-1 binding to rat skeletal muscle

Delgado, Elena; Luque, Miguel Angel Limón; Alcántara, Ana; Trapote, M. A.; Clemente, Felipe; Galera, C.; Valverde, Isabel; Villanueva-Peñacarrillo, María Luisa

doi:10.1016/0196-9781(94)00175-8

Cited by 65 publications

(42 citation statements)

References 28 publications

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“…Nevertheless, in studies involving direct determination of lipolysis rates in human subcutaneous tissue, Bertin et al (16) were unable to find any effects of GLP-1. GLP-1 receptors have also been claimed to be present in rat skeletal muscle (49), and GLP-1 was reported to stimulate glucose metabolism in human myocytes (173). Similar observations were made in studies of L6 myotubes, and there was evidence that the effects were transmitted via receptors distinct from the classical GLP-1 receptor (336).…”

Section: Whole Body Effects Peripheral Effects and Effects On Insupporting

confidence: 68%

The Physiology of Glucagon-like Peptide 1

Holst¹

2007

Physiological Reviews

2,637

2,385

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Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the “ileal brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.

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Section: Whole Body Effects Peripheral Effects and Effects On Insupporting

confidence: 68%

The Physiology of Glucagon-like Peptide 1

Holst¹

2007

Physiological Reviews

2,637

2,385

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“…In vitro studies also suggest that GLP-1 may have extrapancreatic effects (8,9). GLP-1 receptors are present in muscle (10,11), fat (8,12), and liver (13). In vitro studies have shown that GLP-1 can increase glucose uptake in each of these tissues and that its effects are additive to those of insulin (14,15).…”

mentioning

confidence: 98%

Effect of Glucagon-Like Peptide-1(7-36)-Amide on Initial Splanchnic Glucose Uptake and Insulin Action in Humans With Type 1 Diabetes

Vella¹,

Shah²,

Basu³

et al. 2001

Diabetes

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In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at ϳ5.5 mmol/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [3 H]glucose) was infused via an intraduodenal tube at a rate of 20 mol ⅐ kg ؊1 ⅐ min ؊1 . Insulin concentrations were increased to ϳ500 pmol/l while glucose was clamped at ϳ8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-2 H 2 ]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P ‫؍‬ 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 ؎ 1.5 vs. 4.8 ؎ 0.8 mol ⅐ kg ؊1 ⅐ min ؊1 ). On the other hand, flux through the hepatic uridine-diphosphate-glucose pool did not differ between study days (14.2 ؎ 5.5 vs. 13.0 ؎ 4.2 mol ⅐ kg ؊1 ⅐ min ؊1 ), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 ؎ 2.9 vs. 1.3 ؎ 1.4 mol ⅐ kg ؊1 ⅐ min ؊1 ), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 ؎ 10.0 vs. 69.3 ؎ 6.3 mol ⅐ kg ؊1 ⅐ min ؊1 ; P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes. Diabetes 50: 565-572, 2001 G lucagon-like peptide-1(7-36)-amide (GLP-1) and its analogues are being actively evaluated as a potential therapy for humans with type 1 diabetes (1-5). GLP-1 enhances insulin secretion, decreases glucagon secretion, and delays gastric emptying (6,7). In vitro studies also suggest that GLP-1 may have extrapancreatic effects (8,9). GLP-1 receptors are present in muscle (10,11), fat (8,12), and liver (13). In vitro studies have shown that GLP-1 can increase glucose uptake in each of these tissues and that its effects are additive to those of insulin (14,15). In contrast, results from in vivo studies have been less consistent. GLP-1 has been reported to increase glucose uptake during hyperglycemia and hyperinsulinemia in diabetic rats (16) and pancreatectomized dogs (17) and during euglycemia and hyperinsulinemia in humans with type 1 diabetes (18). On the other hand, GLP-1 has been reported to have no effect on insulin action during euglycemia and hyperinsulinemia in nondiabetic humans (19) and dogs (20) or during "prandial" insulin and glucose infusions in humans with type 2 diabetes (21).All of these studies evaluated insulin action during intravenous glucose infusion. This approach contrasts with the situation that occurs und...

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“…also binds [8], have been reported to be present in muscle [9,10], fat [11,12] and the liver [13]. GLP-1 (7-36) can increase glucose uptake in each of these tissues with its effects being additive to those of insulin [12,14,15,16].…”

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confidence: 99%

Lack of effect of exendin-4 and glucagon-like peptide-1-(7,36)-amide on insulin action in non-diabetic humans

et al. 2003

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Aims/hypothesis. The aim of this study was to determine whether rapid conversion to inactive and potentially antagonistic peptides could alter the response to GLP-1. Methods. We evaluated the ability of exendin-4, a GLP-1 analogue resistant to degradation by dipeptidyl peptidase IV, to modulate insulin-induced stimulation of glucose uptake and suppression of glucose production in eight healthy subjects during infusion of GLP-1 (1.2 pmol·kg -1 ·min -1 ), exendin-4 (0.12 pmol·kg -1 · min -1 ), or saline. Glucose was clamped at 5.3 mmol/l and insulin was infused to progressively increase insulin concentrations to about 65, 190 and 700 pmol/l, respectively. Endogenous insulin secretion was inhibited with somatostatin to ensure comparable portal insulin concentrations while glucagon and growth hormone were maintained at basal concentrations. Results. Glucose, insulin, C-peptide, glucagon and growth hormone concentrations did not differ on the three occasions. In contrast, cortisol concentrations were greater during both exendin-4 (25.1±4.4 mmol/l per 7 h; p<0.01) and GLP-1, (17.0±2.0 mmol/l 7 h; p<0.05) than saline (13.5±1.5 mmol/l per 7 h). While insulin-induced stimulation of glucose disappearance at the highest insulin concentrations tended to be greater and insulin-induced suppression of glucose production lower in the presence of exendin-4 or GLP-1 than saline, the differences were not significant. Conclusion/interpretation. Exendin-4 and GLP-1 increase cortisol secretion in human subjects. However, neither alters insulin action in non-diabetic human subjects. These data also suggest that the lack of an effect of GLP-1 on insulin action is not likely to be explained by rapid degradation to inactive or antagonistic peptides. [Diabetologia (2002[Diabetologia ( ) 45:1410[Diabetologia ( -1415 Keywords GLP-1, exendin-4, insulin action, glucose production, cortisol secretion. [11,12] and the liver [13]. GLP-1 (7-36) can increase glucose uptake in each of these tissues with its effects being additive to those of insulin [12,14,15,16]. In contrast, results from in vivo studies have been less consistent. GLP-1 (7-36) has been reported to increase glucose uptake during hyperglycaemia and hyperinsulinaemia in diabetic rats [17], pancreatectomized dogs [18] and in Type I (insulin-dependent) diabetic patients [19,20]. In contrast, GLP-1 (7-36) has been reported to have no effect on the insulin action in non-diabetic human subjects [21] GLP-1 (7-36) is actively being evaluated as a therapy for diabetes mellitus. GLP-1 (7-36) increases insulin secretion, decreases glucagon secretion and delays gastric emptying [1,2,3,4,5,6,7]. In vitro data suggest it might also enhance insulin action. Although controversial, GLP-1 receptors, to which Exendin-4

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Glucagon-like peptide-1 binding to rat skeletal muscle

Cited by 65 publications

References 28 publications

The Physiology of Glucagon-like Peptide 1

The Physiology of Glucagon-like Peptide 1

Effect of Glucagon-Like Peptide-1(7-36)-Amide on Initial Splanchnic Glucose Uptake and Insulin Action in Humans With Type 1 Diabetes

Lack of effect of exendin-4 and glucagon-like peptide-1-(7,36)-amide on insulin action in non-diabetic humans

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