scholarly journals Physiological role of cholecystokinin on postprandial insulin secretion and gastric meal emptying in man. Studies with the cholecystokinin receptor antagonist loxiglumide

Diabetologia ◽  
1991 ◽  
Vol 34 (10) ◽  
pp. 721-726 ◽  
Author(s):  
M. Fried ◽  
W. Schwizer ◽  
C. Beglinger ◽  
U. Keller ◽  
J. B. Jansen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Receptor Antagonist ◽  
Physiological Role ◽  
Cholecystokinin Receptor ◽  
Postprandial Insulin

Role of Endogenously Released Cholecystokinin in Determining Postprandial Insulin Levels in Man: Effects of Loxiglumide, a Specific Cholecystokinin Receptor Antagonist

Digestion ◽  
1992 ◽  
Vol 53 (3-4) ◽  
pp. 189-199 ◽  
Author(s):  
Friedemann Baum ◽  
MichaelA. Nauck ◽  
Reinhold Ebert ◽  
Per Cantor ◽  
Georg Hoffmann ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cholecystokinin Receptor ◽  
Insulin Levels ◽  
Postprandial Insulin

Role of sulfate ester in influencing biologic activity of cholecystokinin-related peptides

1987 ◽  
Vol 252 (2) ◽  
pp. G178-G181 ◽  
Author(s):  
R. Vinayek ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Partial Agonist ◽  
Tyrosine Residue ◽  
Sulfate Ester ◽  
Rat Pancreas ◽  
Cck Receptors ◽  
Cholecystokinin Receptor ◽  
Cholecystokinin Receptors

In dispersed acini from guinea pig, mouse, or rat pancreas cholecystokinin-(27-33) is a full agonist, and removing the sulfate ester from the tyrosine residue in position 27 caused a 100- to 300-fold decrease in potency with no change in efficacy. In dispersed acini from mouse or rat pancreas, cholecystokinin-(27-32)-NH2 is a partial agonist, and removing the sulfate ester from the tyrosine in position 27 abolished the efficacy. The desulfated peptide was able, however, to interact with CCK receptors with a potency that was threefold less than that of cholecystokinin-(27-32)-NH2 and therefore functioned as a cholecystokinin receptor antagonist. In dispersed acini from guinea pig pancreas cholecystokinin-(27-32)-NH2 is a cholecystokinin receptor antagonist. Removing the sulfate ester from the tyrosine residue in position 27 of cholecystokinin(27-32)-NH2 caused a fourfold decrease in potency but did not abolish the ability of the peptide to interact with cholecystokinin receptors; therefore, desulfated cholecystokinin-(27-32)-NH2 functioned as a cholecystokinin receptor antagonist.

Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo

2012 ◽  
Vol 302 (4) ◽  
pp. E403-E408 ◽  
Author(s):  
Mika Bando ◽  
Hiroshi Iwakura ◽  
Hiroyuki Ariyasu ◽  
Hiroshi Hosoda ◽  
Go Yamada ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Medium Chain Triglyceride ◽  
Physiological Role ◽  
Standard Diet ◽  
Entry Site ◽  
Insulin Secretion In Vivo

Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to ∼16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic β-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.

The N-methyl-d-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat

1991 ◽  
Vol 131 (3) ◽  
pp. 435-441 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
E. C. M. van Leeuwen
Keyword(s):  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Acute Treatment ◽  
Physiological Role ◽  
Female Rat ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Serum Lh ◽  
Lh Secretion

ABSTRACT The physiological role of activated hypothalamic N-methyl-d-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0·1–0·2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0·2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0·2, or one injection of 0·5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 × 0·2 mg/kg) or complete (2×0·2 and 1 × 0·5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats that ovulated. Thus chronic blockade of the NMDA receptors by the antagonist MK-801 delays but does not prevent first ovulation, whereas acute treatment blocks the pro-oestrous LH peak. It was concluded that activation of NMDA receptors plays an important role both in tonic and preovulatory LH secretion during the onset of puberty in the female rat. Journal of Endocrinology (1991) 131, 435–441

The Role of GLP-1 7–36 in Control of Insulin Secretion Investigated Using the Receptor Antagonist, Exendin (9–39)

1995 ◽  
Vol 89 (s33) ◽  
pp. 2P-2P
Author(s):  
Zhili Wang ◽  
Renming Wang ◽  
Ali A. Owji ◽  
David M. Smith ◽  
Mohammad A. Ghatei ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Receptor Antagonist

scholarly journals Nuclear Factor Y in Male Mouse pancreatic β-cells Plays a Crucial Role in Glucose Homeostasis by Regulating β-Cell Mass and Insulin Secretion

2021 ◽  
Author(s):  
Yin Liu ◽  
Siyuan He ◽  
Ruixue Zhou ◽  
Xueping Zhang ◽  
Shanshan Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Cell Mass ◽  
Physiological Role ◽  
Nuclear Factor ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Nuclear Factor Y

Pancreatic β-cell mass and insulin secretion are determined by the dynamic change of transcription factor expression levels in response to altered metabolic demand. Nuclear factor-Y (NF-Y) is an evolutionarily conserved transcription factor playing critical roles in multiple cellular processes. However, the physiological role of NF-Y in pancreatic β-cells is poorly understood. The present study was undertaken in a conditional knockout of <i>Nf-ya</i> specifically in pancreatic β-cells (<i>Nf-ya </i>βKO) to define the essential physiological role of NF-Y in β-cells. <i>Nf-ya </i>βKO mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced β-cell proliferation resulting in decreased β-cell mass was observed in these mice, which was associated with disturbed actin cytoskeleton. NF-Y-deficient β-cells also exhibited impaired insulin secretion with a reduced Ca<sup>2+</sup> influx in response to glucose, which was associated an inefficient glucose uptake into β-cells due to a decreased expression of glucose transporter 2 and a reduction in ATP production resulting from the disruption of mitochondrial integrity. This study is the first to show that NF-Y is critical for pancreatic islets homeostasis and function through regulation in β-cell proliferation, glucose uptake into β-cells, and mitochondrial energy metabolism. Modulating NF-Y expression in β-cells may therefore offer an attractive approach for therapeutic intervention.

Evidence for a physiological role for CCK in the regulation of food intake in mice

1989 ◽  
Vol 256 (3) ◽  
pp. R646-R652 ◽  
Author(s):  
A. J. Silver ◽  
J. F. Flood ◽  
A. M. Song ◽  
J. E. Morley
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Food Consumption ◽  
Lever Press ◽  
Physiological Role ◽  
Cholecystokinin Octapeptide ◽  
Cholecystokinin Receptor ◽  
Decrease Food Intake

The effects of L-364,718, a cholecystokinin receptor antagonist, on cholecystokinin octapeptide-induced inhibition of food, and its effect on food intake when given alone, were studied in mice using several different feeding paradigms. In all studies, L-364,718 (100 micrograms/kg, 1.0 mg/kg) reversed the ability of cholecystokinin octapeptide to decrease food intake. L-364,718 enhanced food consumption compared with controls in nonfasted mice (100 microgram/kg) and in prefed mice (50, 100, 250 micrograms/kg). The number of reinforcements, using a lever press, was also enhanced by L-364,718 (100 micrograms/kg) compared with control. In other paradigms, L-364,718 failed to enhance food intake. These results are compatible with the suggestion that cholecystokinin may play a physiological role in the regulation of food intake.

Regulation of insulin secretion by uncoupling protein

2006 ◽  
Vol 34 (5) ◽  
pp. 802-805 ◽  
Author(s):  
C.B. Chan ◽  
N. Kashemsant
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Uncoupling Protein ◽  
Physiological Role ◽  
Atp Production ◽  
Ucp2 Expression ◽  
Increased Sensitivity ◽  
Glucose Stimulated Insulin Secretion

UCPs (uncoupling proteins) can regulate cellular ATP production by uncoupling oxidative phosphorylation. UCP2 is expressed in islet β-cells and its induction reduces glucose-stimulated insulin secretion. Under physiological conditions, superoxide, formed as a by-product of respiration, activates UCP2. This leads to reduced ATP production, which impairs closure of the ATP-dependent K+ channels to prevent insulin secretion. It is suggested that the physiological role of UCP2 is to prevent excessive superoxide generation through a feedback loop. UCP2 induction may also alter fatty acid metabolism by altering NAD/NADH or by facilitating cycling of fatty acid anions. Recently, UCP2 has been proposed to keep insulin secretion low during starvation, a function under the control of the transcription co-repressor, surtuin-1, which has been shown to bind to the UCP2 promoter. Pathological UCP2 expression or activation may suppress glucose-stimulated insulin secretion to the extent that diabetes onset is hastened. In ob/ob mice, induction of UCP2 at age 5 weeks precedes development of insulin secretion defects and hyperglycaemia. Activating protein kinase A-dependent pathways can normalize insulin secretion in UCP2-overexpressing islets. Conversely, lowering UCP2 expression may promote increased insulin secretion. UCP2 knockout mice were protected from the diabetogenic effects of a high-fat diet and their islets exhibited increased sensitivity to glucose and elevated ATP/ADP. These results support a role for UCP2 as a gene contributing to the pathogenesis of Type 2 diabetes.

Sign in / Sign up

Export Citation Format

Share Document