Nateglinide increases first phase insulin secretion and enhances glucose clearance in type 2 diabetes

2000 ◽  
Vol 50 ◽  
pp. 69
Author(s):  
StevenE. Kahn ◽  
Brenda Montgomery ◽  
Monica Ligueros-Saylan ◽  
Chyi-Hung Hsu ◽  
Damayanthi Devineni ◽  
...  
2000 ◽  
Vol 279 (3) ◽  
pp. E520-E528 ◽  
Author(s):  
Thomas Laedtke ◽  
Lise Kjems ◽  
Niels Pørksen ◽  
Ole Schmitz ◽  
Johannes Veldhuis ◽  
...  

Impaired insulin secretion in type 2 diabetes is characterized by decreased first-phase insulin secretion, an increased proinsulin-to-insulin molar ratio in plasma, abnormal pulsatile insulin release, and heightened disorderliness of insulin concentration profiles. In the present study, we tested the hypothesis that these abnormalities are at least partly reversed by a period of overnight suspension of β-cell secretory activity achieved by somatostatin infusion. Eleven patients with type 2 diabetes were studied twice after a randomly ordered overnight infusion of either somatostatin or saline with the plasma glucose concentration clamped at ∼8 mmol/l. Controls were studied twice after overnight saline infusions and then at a plasma glucose concentration of either 4 or 8 mmol/l. We report that in patients with type 2 diabetes, 1) as in nondiabetic humans, insulin is secreted in discrete insulin secretory bursts; 2) the frequency of pulsatile insulin secretion is normal; 3) the insulin pulse mass is diminished, leading to decreased insulin secretion, but this defect can be overcome acutely by β-cell rest with somatostatin; 4) the reported loss of orderliness of insulin secretion, attenuated first-phase insulin secretion, and elevated proinsulin-to-insulin molar ratio also respond favorably to overnight inhibition by somatostatin. The results of these clinical experiments suggest the conclusion that multiple parameters of abnormal insulin secretion in patients with type 2 diabetes mechanistically reflect cellular depletion of immediately secretable insulin that can be overcome by β-cell rest.


2005 ◽  
Vol 22 (10) ◽  
pp. 1408-1413 ◽  
Author(s):  
M. Hollingdal ◽  
J. Sturis ◽  
M.-A. Gall ◽  
P. Damsbo ◽  
S. Pincus ◽  
...  

2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
Author(s):  
Christoffer Martinussen ◽  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Siv H. Jacobsen ◽  
Nils B. Jørgensen ◽  
...  

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.


2017 ◽  
Vol 130 (7) ◽  
pp. 798-804 ◽  
Author(s):  
Li-Heng Meng ◽  
Yao Huang ◽  
Jia Zhou ◽  
Xing-Huan Liang ◽  
Jing Xian ◽  
...  

2012 ◽  
Vol 13 (1) ◽  
pp. 126-139
Author(s):  
K. Cheng ◽  
S. Andrikopoulos ◽  
J. E. Gunton

2013 ◽  
Vol 13 (1) ◽  
pp. 126-139 ◽  
Author(s):  
K. Cheng ◽  
S. Andrikopoulos ◽  
J. E. Gunton

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