Human glucagon‐like peptides 1 and 2 activate rat brain adenylate cyclase

Hoosein, Naseema M.; Gurd, Ruth S.

doi:10.1016/0014-5793(84)81245-4

Cited by 104 publications

(48 citation statements)

References 18 publications

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“…Only few data [7,8] have been reported on biological effects of GLP-1 and GLP-2 which were characterized structurally as nudeotide sequences. The physiological significance of these findings remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…This fact most probably explains the glucagon-and GIP-like action of the peptide on pancreatic islets. However, with regard to the N-terminal extension of GLP-1 beyond the glucagon-like sequence it appears unlikely that the action of GLP-1 is mediated through glucagon receptors [18]; in fact, it has been shown that GLP-1 does not bind to glucagon receptors in the liver [7], so one can speculate that GLP-1 may act on its own or on the GIP-receptor on the pancreatic B-cell which has been recently identified [19].…”

Section: Discussionmentioning

confidence: 99%

“…Two reasons could explain these negative results: First, due to the lack of interaction with the glucagon receptor in the liver [7] no effect on hepatic gluconeogenesis can be ex-pected. Secondly, the authors only investigated the effect of GLP-1 in fasting rabbits, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Very little is known about a specific biological activity of these peptides. Hoosein and Gurd [7] could demonstrate a potent stimulation of rat hypothalamic and pituitary adenylate cyclase, whereas binding of glucagon to rat brain and liver membranes was not inhibited. GLP-1 may exert a weak stimulatory effect on exocrine pancreatic secretion in the rat [8].…”

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confidence: 91%

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Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

1985

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Summary. Glucagon-like peptide-1 and glucagon-like peptide-2 are encoded by the m-RNA of pancreatic preproglucagon. They show high conservation in different species and substantial sequence homology to glucagon. Because no definite biological activity of these peptides has been reported, we investigated the effect of synthetic C-terminally amidated glucagon-like peptide-t [1-36] and synthetic human glucagonlike peptide-2 [1-34] with a free C-terminus on insulin release from isolated precultured rat pancreatic islets in the presence of glucose. Glucagon-like peptide-1 stimulates insulin release at 10 and 16.7 mmol/1 glucose in a dose-dependent manner. Significant stimulation starts at 2.5 nmol/1 in the presence of 10 mmol/1 glucose and near maximal release is observed at 250 nmol/l, with approximately 100% increase over basal at both glucose concentrations. The peptide reaches 63% of the maximal stimulatory effect of glucagon. No stimulation occurs in the presence of 2.8 mmol/1 glucose. Glucagon-like peptide-2 has no effect on insulin secretion at any glucose concentration tested. It is concluded that glucagon-like peptide-t, in contrast to glucagon-like peptide-2, exhibits a glucose-dependent insulinotropic action on isolated rat pancreatic islets similar to that of glucagon and gastric inhibitory polypeptide.Key words: Glucagon-like peptide-t, glucagon-like peptide-2, insulin release, glucose dependency, isolated islets.Pancreatic preproglucagon m-RNA, the precursor of pancreatic glucagon, has been cloned and sequenced from different species using recombinant DNA-techniques [1][2][3][4][5]. Two other peptides have been found arranged in tandem on the same m-RNA in close proximity C-terminal to the glucagon precursor: glucagonlike peptide-I (GLP-1) and glucagon-like peptide-2 (GLP-2) comprising 36 and 34 amino acid residues, respectively. Both peptides show a different degree of sequence homology to pancreatic glucagon. The GLP-1 sequence is identical in the human, bovine and hamster precursor, whereas minor differences exist between the corresponding GLP-2 sequences. This substantial conservation in evolution and the close sequence homology to the glucagon molecule (GLP-I: 48% identical residues; GLP-2: 38%) indicates that GLP-1 and GLP-2 may play an important role of their own as hormones or local modulators. Recently they have been detected by specific radioimmunoassays in glucagonomas and in rat pancreatic islets [6], although they have not to date been isolated at the peptide level. Very little is known about a specific biological activity of these peptides. Hoosein and Gurd [7] could demonstrate a potent stimulation of rat hypothalamic and pituitary adenylate cyclase, whereas binding of glucagon to rat brain and liver membranes was not inhibited. GLP-1 may exert a weak stimulatory effect on exocrine pancreatic secretion in the rat [8].Suggesting a role in carbohydrate metabolism, we investigated the effect of synthetic GLP-I and GLP-2 on insulin release from isolated precultured rat pancreatic islets in th...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

See 2 more Smart Citations

Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

1985

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“…The GLP-1 sequence is identical in hamster, man, ox and rat [2] and this high degree of sequence conservation suggests that GLP-1 has a significant biological role which has yet to be determined. Apart from its weak insulinotropic effect [3], the only known actions of GLP-1 are its binding in the hypothalamus and pituitary and the subsequent adenylate cyclase activation [4,5]. While GLP-1 is the major processed form found in the pancreas a smaller fragment GLP-1 7-36 NHz predominates in the intestine [6].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of glucagon‐like peptide‐1 7–36 amide‐binding sites in the rat brain and lung

et al. 1988

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High-affinity binding sites for glucagon-like peptide-I 7 36 amide (GLP-I 7-36 NH2) were identified in rat brain and lung membranes. Binding of [a25I]GLP-I 7 36 NH z was rapid, reversible, specific, saturable and pH dependent. Specific binding in the central nervous system was particularly high in the hypothalamus and the brain stem. Oxyntomodulin, glucagon-like peptide-l, glucagon-like peptide-2 and glucagon were 100-1000-fold less potent than GLP-I 7-36 NH z in competition for this binding site.Glucagon-like peptide 7-36 amide; Receptor; (Brain, Lung)

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Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system

Merchenthaler¹,

Lane²,

Shughrue³

1999

J. Comp. Neurol.

699

586

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Human glucagon‐like peptides 1 and 2 activate rat brain adenylate cyclase

Cited by 104 publications

References 18 publications

Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

Identification and characterization of glucagon‐like peptide‐1 7–36 amide‐binding sites in the rat brain and lung

Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system

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