scholarly journals Pancreatic Islet APJ Deletion Reduces Islet Density and Glucose Tolerance in Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (7) ◽  
pp. 2451-2460 ◽  
Author(s):  
Song Han ◽  
Ella W. Englander ◽  
Guillermo A. Gomez ◽  
Cristiana Rastellini ◽  
Thomas Quertermous ◽  
...  

Protection and replenishment of a functional pancreatic β-cell mass (BCM) are key goals of all diabetes therapies. Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor. The apelin-APJ signaling system is expressed in rodent and human islet cells. Apelin exposure has been shown to inhibit and to stimulate insulin secretion. Our aim was to assess the influence of a selective APJ deletion in pancreatic islet cells on islet homeostasis and glucose tolerance in mice. Cre-LoxP strategy was utilized to mediate islet APJ deletion. APJ deletion in islet cells (APJΔislet) resulted in a significantly reduced islet size, density and BCM. An ip glucose tolerance test showed significantly impaired glucose clearance in APJΔislet mice. APJΔislet mice were not insulin resistant and in vivo glucose-stimulated insulin secretion was reduced modestly. In vitro glucose-stimulated insulin secretion showed a significantly reduced insulin secretion by islets from APJΔislet mice. Glucose clearance in response to ip glucose tolerance test in obese APJΔislet mice fed a chronic high-fat (HF) diet, but not pregnant APJΔislet mice, was impaired significantly. In addition, the obesity-induced adaptive elevations in mean islet size and fractional islet area were reduced significantly in obese APJΔislet mice when compared with wild-type mice. Together, these findings demonstrate a stimulatory role for the islet cell apelin-APJ signaling axis in regulation of pancreatic islet homeostasis and in metabolic induced β-cell hyperplasia. The results indicate the apelin-APJ system can be exploited for replenishment of BCM.

2011 ◽  
Vol 165 (1) ◽  
pp. 69-76 ◽  
Author(s):  
A Battezzati ◽  
A Mari ◽  
L Zazzeron ◽  
G Alicandro ◽  
L Claut ◽  
...  

BackgroundCystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.AimTo evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.MethodsA total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.ResultsFifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6 pmol/min per m2 per mM, P<0.001) and decreased significantly with age by −2.7 pmol/min per m2 per mM per year (confidence interval (CI) −4.5 to −0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.ConclusionThe major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.


1960 ◽  
Vol XXXIII (II) ◽  
pp. 157-167
Author(s):  
T. Rodari ◽  
G. Specchia

ABSTRACT The double intravenous glucose tolerance test does not modify the assimilation coefficient in normal and thin diabetic subjects. On the contrary, in fat diabetic subjects the second coefficient of assimilation increases significantly, but not the first one. From these researches it is evident that the valuation of glucose assimilation by double venous hyperglycaemic test indicates the functional behaviour of the pancreas in different diabetic states. The interpretation of this behaviour of pancreatic islet response to the double venous hyperglycaemic test is discussed.


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