Demonstration that the vitamin D metabolite 1,25(OH)2-vitamin D3 and not 24R,25(OH)2-vitamin D3 is essential for normal insulin secretion in the perfused rat pancreas

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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Effect of Corticosterone on Carbamylcholine-, Leucine-, or Calcium-Induced Insulin Secretion by the Isolated Perfused Rat Pancreas*

Endocrinology ◽

10.1210/endo-114-4-1086 ◽

1984 ◽

Vol 114 (4) ◽

pp. 1086-1089 ◽

Cited By ~ 3

Author(s):

GEGHAM BARSEGHIAN ◽

CYNTHIA TOMKINSON ◽

DAVID L. HWANG ◽

ARYE LEV-RAN

Keyword(s):

Insulin Secretion ◽

Perfused Rat Pancreas ◽

Rat Pancreas ◽

Isolated Perfused Rat Pancreas

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Minimal modeling of insulin secretion in the perfused rat pancreas: a drug effect case study

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00603.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. E627-E634 ◽

Cited By ~ 8

Author(s):

Michela Riz ◽

Morten Gram Pedersen ◽

Gianna Maria Toffolo ◽

Guido Haschke ◽

Hans-Christoph Schneider ◽

...

Keyword(s):

Insulin Secretion ◽

Minimal Model ◽

Cell Function ◽

Fold Increase ◽

Second Phase ◽

Good Precision ◽

Β Cell ◽

Perfused Rat Pancreas ◽

Rat Pancreas ◽

Β Cell Function

The experimental protocol of the perfused rat pancreas is commonly used to evaluate β-cell function. In this context, mathematical models become useful tools through the determination of indexes that allow the assessment of β-cell function in different experimental groups and the quantification of the effects of antidiabetic drugs, secretagogues, or treatments. However, a minimal model applicable to the isolated perfused rat pancreas has so far been unavailable. In this work, we adapt the C-peptide minimal model applied previously to the intravenous glucose tolerance test to obtain a specific model for the experimental settings of the perfused pancreas. Using the model, it is possible to estimate indexes describing β-cell responsivity for first (ΦD) and second phase (ΦS, T) of insulin secretion. The model was initially applied to untreated pancreata and afterward used for the assessment of pharmacologically relevant agents (the gut hormone GLP-1, the potent GLP-1 receptor agonist lixisenatide, and a GPR40/FFAR1 agonist, SAR1) to quantify and differentiate their effect on insulin secretion. Model fit was satisfactory, and parameters were estimated with good precision for both untreated and treated pancreata. Model application showed that lixisenatide reaches improvement of β-cell function similarly to GLP-1 (11.7- vs. 13.1-fold increase in ΦD and 2.3- vs. 2.8-fold increase in ΦS) and demonstrated that SAR1 leads to an additional improvement of β-cell function in the presence of postprandial GLP-1 levels.

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