Glucagon-like peptide-1 does not have a role in hepatic carbohydrate metabolism

Ghiglione, M.; Blázquez, Enrique; Uttenthal, L. O.; Diego, Juana Gutiérrez de; Álvarez, Elvira; George, S. K.; Bloom, Stephen R.

doi:10.1007/bf00703137

Cited by 40 publications

(22 citation statements)

References 11 publications

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“…Searching for possible effects of GLP-1 on glucose metabolism Ghiglione et al and Shimizu, Hirota, Ohboshi & Shima failed to demonstrate specific binding sites on rat liver membranes [62,63]. Furthermore, GLP-l(7-36) amide did not interact with glucagon receptors, in accordance to a previous study published by Hoosein & Gurd [64].…”

Section: Glp-1 and Liversupporting

confidence: 61%

Glucagon‐like peptide‐1(7–36) amide is a new incretin/enterogastrone candidate

Göke

Fehmann

Göke

1991

Eur J Clin Investigation

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Section: Glp-1 and Liversupporting

confidence: 61%

Glucagon‐like peptide‐1(7–36) amide is a new incretin/enterogastrone candidate

Göke

Fehmann

Göke

1991

Eur J Clin Investigation

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“…In fish hepatocytes GLPs stimulate gluconeogenesis, but they do not employ cAMP as an intracellular messenger [13], In rat liver the larger amino terminally-extended peptide GLP-I (1-371 does not alter glucagon-mediated production of cAMP [14] nor does it stimulate insulin release at all [1] or only weakly [15]. Because the short …”

Section: Introductionmentioning

confidence: 99%

Absence of insulinotropic glucagon‐like peptide‐I(7–37) receptors on isolated rat liver hepatocytes

et al. 1991

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The effect~ of lglucagon and the llluc, tlon-like I'.cptide GLP-1(7=37) were compared in rat liver hepatocytes. Gluea¢8on elevated cAMP, elevated intracell ular free calcium {ICon*J0, activated phosphoryht~ and stin)t=lated illu¢oneogenesi~, wherea~ GLP.I(?~37) was without effect on any of the~¢ parameters, GLP-1:(7=37] did not block any of the actions of glaeagon, The lllucaBon analog, de( Hi,= t IGItP] glucagon an'tide, was a partial agonist in liver, but al~o was an effective antagonist of Illucagon actions in liver but not those of GLP.I (7=37J ht islet B cells, It was cone}uded that in the rat, GLP-1(7=37) is a potent Insulin secrelailogue Ill but is without effect on liver,

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“…GLP-1 receptors have been reported to be present in fat, muscle, and liver (10)(11)(12)(13). Some (14-17), but not all (18), in vitro studies have shown that GLP-1 can stimulate glucose uptake and enhance insulin action in these tissues. In vivo studies have been even more contradictory.…”

mentioning

confidence: 99%

Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes.

et al. 2000

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Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose eff e c t i v eness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 p m o l · k g -1 · min -1 ) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal (1.21 ± 0.15 vs. 1.32 ± 0 . 1 9 mol/l per 6 h) and prandial (0.56 ± 0.14 vs. 0.56 ± 0 . 1 0 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 ± 0.3 vs. -3.1 ± 0.2 µmol/kg) and prandial (-3.1 ± 0.4 vs. -3.0 ± 0.6 µmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, G L P-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism. D i a b e t e s 4 9 :6 1 1-617, 2000 P eople with type 2 diabetes have defects in insulin secretion, insulin action, and glucose effectiveness ( d e fined as the ability of glucose to stimulate its own uptake and suppress its own release at basal insulin). Numerous studies have established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulus for insulin secretion in both people with type 2 diabetes and healthy volunteers (1-5). It also inhibits glucagon secretion and delays gastric emptying (3,6,7). However, GLP-1's effects on insulin action and glucose effectiveness are more controversial (8,9). GLP-1 receptors have been reported to be present in fat, muscle, and liver (10-13). Some (14-17), but not all (18), in vitro studies have shown that GLP-1 can stimulate glucose uptake and enhance insulin action in these tissues. In vivo studies have been even more contradictory. Gutniak et al. (19) and Sandhu et al. (20) have reported that GLP-1 increases glucose uptake during a hyperinsulinemic-euglycemic clamp in people with t y p e 1 diabetes and in pancreatec...

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Glucagon-like peptide-1 does not have a role in hepatic carbohydrate metabolism

Cited by 40 publications

References 11 publications

Glucagon‐like peptide‐1(7–36) amide is a new incretin/enterogastrone candidate

Glucagon‐like peptide‐1(7–36) amide is a new incretin/enterogastrone candidate

Absence of insulinotropic glucagon‐like peptide‐I(7–37) receptors on isolated rat liver hepatocytes

Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes.

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