In vivo biological activity of exendin (1-30)

Máire E. Doyle; Patrick McConville; Michael J. Theodorakis; Margaret M. Goetschkes; Michel Bernier; Richard G.S. Spencer; Harold W. Holloway; Nigel H. Greig; Josephine M. Egan

In vivo biological activity of exendin (1-30)

Máire E. Doyle, Patrick McConville, Michael J. Theodorakis, Margaret M. Goetschkes, Michel Bernier, Richard G.S. Spencer, Harold W. Holloway, Nigel H. Greig, Josephine M. Egan

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 (a more potent and stable agonist of the GLP-1 receptor than GLP-1) increases insulin secretion. Exendin-4 is 39 amino acids long, unlike GLP-1 which has 30 amino acids. Because of its non-mammalian (lizard) origin and unique C-terminal sequence, exendin-4 may be immunogenic in humans. We showed previously that the C terminally truncated exendin peptide exendin (1-30) has a reduced affinity for the GLP-1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells. Here we show that daily intraperitoneal injection of exendin (1-30) (1 nmol/kg) for 20 d followed by 31 d twice daily to Lepr^db/Lepr^db (db/db) mice significantly reduced the amount of visceral fat relative to saline-treated controls and improved HbA_1C (control 9.5 ± 0.2% vs treated 7.9 ± 0.2%, p = 0.001) but was not as effective as exendin-4. To examine the ability of exendin (1-30) to stimulate beta-cell growth, we injected one group of 3-mo-old Fisher rats with exendin (1-30) (1 nmol/kg) and another group with saline for 8 d. We observed no change in beta-cell area, but did see a change in the number of islets with nuclei positive for BrdU [10.7 ± 1.8% exendin (1-30) vs 6.5 ± 0.5% control].

Original language	English (US)
Pages (from-to)	1-9
Number of pages	9
Journal	Endocrine
Volume	27
Issue number	1
State	Published - Jun 2005
Externally published	Yes

Keywords

Diabetes
Insulinotropic compounds
Magnetic resonance imaging
Rodents

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

Cite this

@article{73d315bbe16049ad804f39dfadf85148,

title = "In vivo biological activity of exendin (1-30)",

abstract = "Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 (a more potent and stable agonist of the GLP-1 receptor than GLP-1) increases insulin secretion. Exendin-4 is 39 amino acids long, unlike GLP-1 which has 30 amino acids. Because of its non-mammalian (lizard) origin and unique C-terminal sequence, exendin-4 may be immunogenic in humans. We showed previously that the C terminally truncated exendin peptide exendin (1-30) has a reduced affinity for the GLP-1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells. Here we show that daily intraperitoneal injection of exendin (1-30) (1 nmol/kg) for 20 d followed by 31 d twice daily to Leprdb/Leprdb (db/db) mice significantly reduced the amount of visceral fat relative to saline-treated controls and improved HbA1C (control 9.5 ± 0.2% vs treated 7.9 ± 0.2%, p = 0.001) but was not as effective as exendin-4. To examine the ability of exendin (1-30) to stimulate beta-cell growth, we injected one group of 3-mo-old Fisher rats with exendin (1-30) (1 nmol/kg) and another group with saline for 8 d. We observed no change in beta-cell area, but did see a change in the number of islets with nuclei positive for BrdU [10.7 ± 1.8% exendin (1-30) vs 6.5 ± 0.5% control].",

keywords = "Diabetes, Insulinotropic compounds, Magnetic resonance imaging, Rodents",

author = "Doyle, {M{\'a}ire E.} and Patrick McConville and Theodorakis, {Michael J.} and Goetschkes, {Margaret M.} and Michel Bernier and Spencer, {Richard G.S.} and Holloway, {Harold W.} and Greig, {Nigel H.} and Egan, {Josephine M.}",

note = "Funding Information: Without the positive on-going support of our scientific director, Dr. D. L. Longo, these studies would not have been conducted. Michael J. Theodorakis was supported by a Clin PRAT Fellowship from the National Institute of General Medical Sciences and the NIH Clinical Center, Bethesda, MD. The current address of Patrick McConville is Molecular Imaging Research, Inc. (MIR), 924 North Main Street, Ann Arbor, MI 48104.",

year = "2005",

month = jun,

language = "English (US)",

volume = "27",

pages = "1--9",

journal = "Endocrine",

issn = "1355-008X",

publisher = "Humana Press",

number = "1",

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TY - JOUR

T1 - In vivo biological activity of exendin (1-30)

AU - Doyle, Máire E.

AU - McConville, Patrick

AU - Theodorakis, Michael J.

AU - Goetschkes, Margaret M.

AU - Bernier, Michel

AU - Spencer, Richard G.S.

AU - Holloway, Harold W.

AU - Greig, Nigel H.

AU - Egan, Josephine M.

N1 - Funding Information: Without the positive on-going support of our scientific director, Dr. D. L. Longo, these studies would not have been conducted. Michael J. Theodorakis was supported by a Clin PRAT Fellowship from the National Institute of General Medical Sciences and the NIH Clinical Center, Bethesda, MD. The current address of Patrick McConville is Molecular Imaging Research, Inc. (MIR), 924 North Main Street, Ann Arbor, MI 48104.

PY - 2005/6

Y1 - 2005/6

N2 - Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 (a more potent and stable agonist of the GLP-1 receptor than GLP-1) increases insulin secretion. Exendin-4 is 39 amino acids long, unlike GLP-1 which has 30 amino acids. Because of its non-mammalian (lizard) origin and unique C-terminal sequence, exendin-4 may be immunogenic in humans. We showed previously that the C terminally truncated exendin peptide exendin (1-30) has a reduced affinity for the GLP-1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells. Here we show that daily intraperitoneal injection of exendin (1-30) (1 nmol/kg) for 20 d followed by 31 d twice daily to Leprdb/Leprdb (db/db) mice significantly reduced the amount of visceral fat relative to saline-treated controls and improved HbA1C (control 9.5 ± 0.2% vs treated 7.9 ± 0.2%, p = 0.001) but was not as effective as exendin-4. To examine the ability of exendin (1-30) to stimulate beta-cell growth, we injected one group of 3-mo-old Fisher rats with exendin (1-30) (1 nmol/kg) and another group with saline for 8 d. We observed no change in beta-cell area, but did see a change in the number of islets with nuclei positive for BrdU [10.7 ± 1.8% exendin (1-30) vs 6.5 ± 0.5% control].

AB - Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 (a more potent and stable agonist of the GLP-1 receptor than GLP-1) increases insulin secretion. Exendin-4 is 39 amino acids long, unlike GLP-1 which has 30 amino acids. Because of its non-mammalian (lizard) origin and unique C-terminal sequence, exendin-4 may be immunogenic in humans. We showed previously that the C terminally truncated exendin peptide exendin (1-30) has a reduced affinity for the GLP-1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells. Here we show that daily intraperitoneal injection of exendin (1-30) (1 nmol/kg) for 20 d followed by 31 d twice daily to Leprdb/Leprdb (db/db) mice significantly reduced the amount of visceral fat relative to saline-treated controls and improved HbA1C (control 9.5 ± 0.2% vs treated 7.9 ± 0.2%, p = 0.001) but was not as effective as exendin-4. To examine the ability of exendin (1-30) to stimulate beta-cell growth, we injected one group of 3-mo-old Fisher rats with exendin (1-30) (1 nmol/kg) and another group with saline for 8 d. We observed no change in beta-cell area, but did see a change in the number of islets with nuclei positive for BrdU [10.7 ± 1.8% exendin (1-30) vs 6.5 ± 0.5% control].

KW - Diabetes

KW - Insulinotropic compounds

KW - Magnetic resonance imaging

KW - Rodents

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AN - SCOPUS:23444435671

SN - 1355-008X

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JO - Endocrine

JF - Endocrine

IS - 1

ER -

In vivo biological activity of exendin (1-30)

Abstract

Keywords

ASJC Scopus subject areas

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