Glucagon responses of isolated α cells to glucose, insulin, somatostatin, and leptin

Lijun Chen, Jacques Philippe, Roger H Unger

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objective: To determine whether glucagon suppression by leptin represents a direct effect on α cells rather than an indirect effect mediated via the hypothalamus. Methods: We devised an in vitro α-cell suppression assay in cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus containing mouse leptin receptors, and they were then incubated with leptin, insulin, or somatostatin in concentrations known to suppress glucagon in vivo. Results: Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect. This inability of leptin to suppress glucagon in vitro could signify that it acts indirectly by causing the release of glucagon-suppressing peptides from the hypothalamus or stomach. To search for such a peptide, we studied the effects on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone, neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and Agouti-related peptide that might be involved in the hypothalamic action of leptin. None of these peptides suppressed glucagon at low, normal, or elevated glucose concentrations. Conclusions: If the cultured α cells used faithfully mimic the leptin response of in situ α cells of the diabetic animal, the glucagon-suppressing action of leptin is indirect, but is not mediated by any 1 of the 6 neuropeptides tested.

Original languageEnglish (US)
Pages (from-to)819-825
Number of pages7
JournalEndocrine Practice
Volume17
Issue number5
DOIs
StatePublished - Sep 1 2011

Fingerprint

Leptin
Somatostatin
Glucagon
Insulin
Glucose
Peptides
Neuropeptides
Cricetinae
Hypothalamus
Melanocyte-Stimulating Hormones
Neurotensin
Neuropeptide Y
Amphetamine
Cocaine
Adenoviridae
Cultured Cells
Stomach

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucagon responses of isolated α cells to glucose, insulin, somatostatin, and leptin. / Chen, Lijun; Philippe, Jacques; Unger, Roger H.

In: Endocrine Practice, Vol. 17, No. 5, 01.09.2011, p. 819-825.

Research output: Contribution to journalArticle

@article{9e1aa0e5d87f48bdb04e0ce897ca0b56,
title = "Glucagon responses of isolated α cells to glucose, insulin, somatostatin, and leptin",
abstract = "Objective: To determine whether glucagon suppression by leptin represents a direct effect on α cells rather than an indirect effect mediated via the hypothalamus. Methods: We devised an in vitro α-cell suppression assay in cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus containing mouse leptin receptors, and they were then incubated with leptin, insulin, or somatostatin in concentrations known to suppress glucagon in vivo. Results: Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect. This inability of leptin to suppress glucagon in vitro could signify that it acts indirectly by causing the release of glucagon-suppressing peptides from the hypothalamus or stomach. To search for such a peptide, we studied the effects on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone, neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and Agouti-related peptide that might be involved in the hypothalamic action of leptin. None of these peptides suppressed glucagon at low, normal, or elevated glucose concentrations. Conclusions: If the cultured α cells used faithfully mimic the leptin response of in situ α cells of the diabetic animal, the glucagon-suppressing action of leptin is indirect, but is not mediated by any 1 of the 6 neuropeptides tested.",
author = "Lijun Chen and Jacques Philippe and Unger, {Roger H}",
year = "2011",
month = "9",
day = "1",
doi = "10.4158/EP11101.OR",
language = "English (US)",
volume = "17",
pages = "819--825",
journal = "Endocrine Practice",
issn = "1530-891X",
publisher = "American Association of Clinical Endocrinology",
number = "5",

}

TY - JOUR

T1 - Glucagon responses of isolated α cells to glucose, insulin, somatostatin, and leptin

AU - Chen, Lijun

AU - Philippe, Jacques

AU - Unger, Roger H

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Objective: To determine whether glucagon suppression by leptin represents a direct effect on α cells rather than an indirect effect mediated via the hypothalamus. Methods: We devised an in vitro α-cell suppression assay in cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus containing mouse leptin receptors, and they were then incubated with leptin, insulin, or somatostatin in concentrations known to suppress glucagon in vivo. Results: Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect. This inability of leptin to suppress glucagon in vitro could signify that it acts indirectly by causing the release of glucagon-suppressing peptides from the hypothalamus or stomach. To search for such a peptide, we studied the effects on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone, neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and Agouti-related peptide that might be involved in the hypothalamic action of leptin. None of these peptides suppressed glucagon at low, normal, or elevated glucose concentrations. Conclusions: If the cultured α cells used faithfully mimic the leptin response of in situ α cells of the diabetic animal, the glucagon-suppressing action of leptin is indirect, but is not mediated by any 1 of the 6 neuropeptides tested.

AB - Objective: To determine whether glucagon suppression by leptin represents a direct effect on α cells rather than an indirect effect mediated via the hypothalamus. Methods: We devised an in vitro α-cell suppression assay in cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus containing mouse leptin receptors, and they were then incubated with leptin, insulin, or somatostatin in concentrations known to suppress glucagon in vivo. Results: Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect. This inability of leptin to suppress glucagon in vitro could signify that it acts indirectly by causing the release of glucagon-suppressing peptides from the hypothalamus or stomach. To search for such a peptide, we studied the effects on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone, neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and Agouti-related peptide that might be involved in the hypothalamic action of leptin. None of these peptides suppressed glucagon at low, normal, or elevated glucose concentrations. Conclusions: If the cultured α cells used faithfully mimic the leptin response of in situ α cells of the diabetic animal, the glucagon-suppressing action of leptin is indirect, but is not mediated by any 1 of the 6 neuropeptides tested.

UR - http://www.scopus.com/inward/record.url?scp=80054084629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054084629&partnerID=8YFLogxK

U2 - 10.4158/EP11101.OR

DO - 10.4158/EP11101.OR

M3 - Article

C2 - 21940282

AN - SCOPUS:80054084629

VL - 17

SP - 819

EP - 825

JO - Endocrine Practice

JF - Endocrine Practice

SN - 1530-891X

IS - 5

ER -