Circadian orchestration of insulin and glucagon release

Abstract α cell function is impaired in diabetes. In diabetics, plasma levels of glucagon are high despite persistently elevated glucose levels and may even rise paradoxically in response to a glucose load; high plasma glucagon levels are accompanied by increased proglucagon gene expression. We have investigated the effects of high glucose concentrations on InR1G9 cells, a glucagon-producing cell line. We show here that chronically elevated glucose concentrations increase glucagon release by 2.5- to 4-fold, glucagon cell content by 2.5- to 3-fold, and proglucagon messenger RNA levels by 4- to 8-fold, whereas changes for 24 h have no effect on proglucagon messenger RNA levels. Persistently elevated glucose affects proglucagon gene expression at the level of transcription and insulin is capable of preventing this effect. We conclude that chronically elevated glucose may be an important factor in the α cell dysfunction that occurs in diabetes and thus that glucose may not only affect the β cell but also the α cell.

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Effect of Islets-Activating Protein of Bordetella Pertussis on Glucagon Release from Mice Isolated Islets

Hormone and Metabolic Research ◽

10.1055/s-2007-1019386 ◽

1981 ◽

Vol 13 (12) ◽

pp. 713-714

Author(s):

R. Kikkawa ◽

M. Haneda ◽

I. Hatanaka ◽

Y. Shigeta ◽

T. Ueno ◽

...

Keyword(s):

Bordetella Pertussis ◽

Isolated Islets ◽

Glucagon Release

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Insulin and Glucagon Release from Isolated Islets of Langerhans: Effect of Enteric Factors

Diabetes ◽

10.2337/diab.18.6.381 ◽

1969 ◽

Vol 18 (6) ◽

pp. 381-386 ◽

Cited By ~ 33

Author(s):

K. D. Buchanan ◽

J. E. Vance ◽

R. H. Williams

Keyword(s):

Islets Of Langerhans ◽

Isolated Islets ◽

Glucagon Release ◽

Isolated Islets Of Langerhans

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Endogenous hyperglycemia restores insulin release impaired by somatostatin analogue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.240.4.e407 ◽

1981 ◽

Vol 240 (4) ◽

pp. E407-E413

Author(s):

G. J. Taborsky ◽

D. Porte

Keyword(s):

Diabetes Mellitus ◽

Insulin Release ◽

Beta Cell Function ◽

Cell Function ◽

Dependent Diabetes Mellitus ◽

Somatostatin Analogue ◽

Base Line ◽

Glucagon Release ◽

Insulin Deficiency ◽

Insulin Responses

These studies assessed the ability of des-Asn5-[D-Trp8-D-Ser13]-somatostatin (d-ATS-SS) to selectively inhibit insulin release and produce a hyperglycemia sufficient to compensate for the original impairment. d-ATS-SS at 0.017 micrograms/min inhibited basal insulin output (delta = -38 +/- 6%, P less than 0.005) and increased basal pancreatic glucagon output (delta - +21 +/- 6%, P less than 0.05, n = 5). d-ATS-SS at 0.17 micrograms/min markedly inhibited insulin output (delta = -84 +/- 4%, P less than 0.0005) and slightly inhibited glucagon output (delta = -14 +/- 6%, P less than 0.05, n = 5). d-ATS-SS at 0.055 micrograms/min decreased basal and stimulated insulin release but not basal nor stimulated glucagon release. By 3.5 of analogue infusion, plasma glucose had risen by 116 +/- 13 mg/dl, and base-line insulin levels and the insulin responses to both isoproterenol and arginine, but not glucose, increased toward control values. We conclude that d-ATS-SS produces selective insulinopenia resulting in hyperglycemia which in turn compensates for the original impairment. Thus, the hyperglycemia observed in other states of selective insulin deficiency (e.g., noninsulin-dependent diabetes mellitus) may compensate for defects in beta-cell function.

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Effects of PHI on hormonal secretion from perfused rat pancreas

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.245.4.e313 ◽

1983 ◽

Vol 245 (4) ◽

pp. E313-E317

Author(s):

J. Szecowka ◽

D. Tendler ◽

S. Efendic

Keyword(s):

Amino Acids ◽

Insulin Secretion ◽

Glucagon Release ◽

The Novel ◽

Perfused Rat Pancreas ◽

Rat Pancreas ◽

Isolated Perfused Rat Pancreas ◽

Hormonal Secretion ◽

D Cells

Effects of the novel gastrointestinal polypeptide PHI with N-terminal histidine, C-terminal isoleucine amide, and 27 amino acids have been studied in isolated perfused rat pancreas. PHI increased the release of insulin, glucagon, and somatostatin. The amounts of these hormones released were strictly dependent on the prevailing glucose concentrations. In the absence of glucose, PHI (1 nmol/liter) stimulated glucagon release. In the presence of 4.4 and 6.7 mmol/liter glucose, the same dose of this peptide stimulated insulin and somatostatin release. In the presence of 16.7 mmol/liter glucose, only insulin secretion was increased by PHI. When arginine was used as a secretagogue, PHI (10 nmol/liter) potentiated secretion of insulin, glucagon, and somatostatin. Thus, PHI may take part in the regulation of the function of the pancreatic A, B, and D cells.

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