scholarly journals Reduced first-phase insulin secretion increases postprandial lipidemia in subjects with impaired glucose tolerance

2017 ◽  
Vol 5 (1) ◽  
pp. e000344 ◽  
Author(s):  
Miguel Ángel Gómez-Sámano ◽  
Daniel Cuevas-Ramos ◽  
Mariana Grajales-Gómez ◽  
Marco Escamilla-Márquez ◽  
Angelina López-Estrada ◽  
...  
Author(s):  
Mark H. Oliver ◽  
Frank H. Bloomfield ◽  
Amita Bansal ◽  
Hui Hui Phua ◽  
Eric B. Thorstensen ◽  
...  

Abstract Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.


2008 ◽  
Vol 295 (2) ◽  
pp. E401-E406 ◽  
Author(s):  
Muhammad A. Abdul-Ghani ◽  
Masafumi Matsuda ◽  
Rucha Jani ◽  
Christopher P. Jenkinson ◽  
Dawn K. Coletta ◽  
...  

To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT ( n = 293) and IGT ( n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as ΔISR/ΔG ÷ IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(−0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0–30 min) was correlated with the increase in FPG in both NGT and IGT ( r = −0.43, P < 0.0001 and r = −0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60–120 min) and FPG was not significant. In conclusion, small increments in FPG, within the “normal” range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.


1998 ◽  
Vol 83 (9) ◽  
pp. 3350-3356 ◽  
Author(s):  
Bo Ahrén ◽  
Giovanni Pacini

This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness (SG), and hepatic extraction (HE) of insulin are altered by age when glucose tolerance is normal. A frequently sampled iv glucose tolerance test was performed in 20 elderly (E, 10/10 male/female, all 63 yr old) and in 20 young subjects (Y, 10/10 male/female, all 27 yr old), who were similar in body mass index and 2-h blood glucose during oral glucose tolerance test. E exhibited impaired glucose elimination (iv tolerance index, 1.31 ± 0.10 vs. 1.70 ± 0.12% min−1; P = 0.019). First-phase insulin secretion and SI did not differ between the groups, whereas E had lower glucose sensitivity of second-phase insulin secretion (0.40 ± 0.07 vs. 0.70 ± 0.08 (pmol/L)min−2/(mmol/L), P = 0.026), lower SG, 0.017 ± 0.002 vs. 0.025± 0.002 min−1, P = 0.004), and higher HE (81.3 ± 2.4 vs. 73.2 ± 2.1%, P = 0.013). Across both groups, SG correlated positively with glucose tolerance index (r = 0.58, P &lt; 0.001) and negatively with HE (r =− 0.54, P &lt; 0.001). Plasma leptin and glucagon did not change by age, whereas plasma pancreatic polypeptide (PP) was higher in E (122 ± 18 vs.66 ± 6 pg/mL, P = 0.004). PP did not, however, correlate to any other parameter. We conclude that E subjects with normal oral glucose tolerance have reduced SG, impaired second-phase insulin secretion, and increased HE, whereas SI and first-phase insulin secretion seem normal. SG seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute.


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.


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