scholarly journals Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes

2014 ◽  
Vol 306 (4) ◽  
pp. G301-G309 ◽  
Author(s):  
Sara Chowdhury ◽  
Dominic N. Reeds ◽  
Dan L. Crimmins ◽  
Bruce W. Patterson ◽  
Erin Laciny ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Gastric Emptying ◽  
Postprandial Glucose ◽  
Nerve Fibers ◽  
Intense Staining ◽  
Glucose Levels ◽  
Healthy Humans ◽  
Glucagon Like Peptide 1

Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10–14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol·kg−1·min−1 was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions.

scholarly journals Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers

2001 ◽  
Vol 281 (1) ◽  
pp. E155-E161 ◽  
Author(s):  
C. Mark B. Edwards ◽  
Sarah A. Stanley ◽  
Rachel Davis ◽  
Audrey E. Brynes ◽  
Gary S. Frost ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Healthy Volunteers ◽  
Plasma Glucose ◽  
Postprandial Glucose ◽  
Calorie Intake ◽  
Glucose Levels ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1) receptor and may be useful in the treatment of type 2 diabetes and obesity. We examined the effects of an intravenous infusion of exendin-4 (0.05 pmol · kg−1 · min−1) compared with a control saline infusion in healthy volunteers. Exendin-4 reduced fasting plasma glucose levels and reduced the peak change of postprandial glucose from baseline (exendin-4, 1.5 ± 0.3 vs. saline, 2.2 ± 0.3 mmol/l, P < 0.05). Gastric emptying was delayed, as measured by the paracetamol absorption method. Volunteers consumed 19% fewer calories at a free-choice buffet lunch with exendin-4 (exendin-4, 867 ± 79 vs. saline 1,075 ± 93 kcal, P = 0.012), without reported side effects. Thus our results are in accord with the possibility that exendin-4 may be a potential treatment for type 2 diabetes, particularly for obese patients, because it acts to reduce plasma glucose at least partly by a delay in gastric emptying, as well as by reducing calorie intake.

scholarly journals Effects of a D-Xylose Preload With or Without Sitagliptin on Gastric Emptying, Glucagon-Like Peptide-1, and Postprandial Glycemia in Type 2 Diabetes

Diabetes Care ◽  
2013 ◽  
Vol 36 (7) ◽  
pp. 1913-1918 ◽  
Author(s):  
T. Wu ◽  
M. J. Bound ◽  
B. R. Zhao ◽  
S. D. Standfield ◽  
M. Bellon ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Postprandial Glycemia ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

iGlarLixi: A Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide for the Treatment of Type 2 Diabetes

2017 ◽  
Vol 51 (11) ◽  
pp. 990-999 ◽  
Author(s):  
Jennifer Goldman ◽  
Jennifer M. Trujillo
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
English Language ◽  
Data Extraction ◽  
Safety Data ◽  
Fixed Ratio ◽  
Postprandial Glucose ◽  
The United States ◽  
Glucagon Like Peptide 1

Objective: To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist. Data Sources: A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed. Study Selection and Data Extraction: All studies assessing the efficacy and/or safety of iGlarLixi were evaluated. Data Synthesis: iGlarLixi has been approved in the United States for glycemic control in people with type 2 diabetes (T2D) inadequately controlled with basal insulin (<60 U/d) or lixisenatide. In clinical trials, iGlarLixi was associated with significantly greater reductions from baseline in glycated hemoglobin A1C (A1C) than iGlar or lixisenatide alone. Reductions in postprandial glucose were also greater with iGlarLixi than with iGlar or lixisenatide. iGlarLixi was weight neutral compared with the weight gain with iGlar and loss with lixisenatide alone, and there was no increase in hypoglycemia with iGlarLixi compared with iGlar despite the greater A1C reduction. Gastrointestinal events, frequently associated with lixisenatide, were less common with iGlarLixi. Potential drawbacks of iGlarLixi include reduced flexibility in dosing and the absence of long-term efficacy and safety data. Conclusions: iGlarLixi is a titratable fixed-ratio combination that shows improved efficacy and comparable or improved safety outcomes relative to its separate constituents, offering an alternative approach to intensification of therapy in T2D.

scholarly journals Teucrium polium: Potential Drug Source for Type 2 Diabetes Mellitus

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 128
Author(s):  
Yaser Albadr ◽  
Andrew Crowe ◽  
Rima Caccetta
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Teucrium Polium

The prevalence of type 2 diabetes mellitus is rising globally and this disease is proposed to be the next pandemic after COVID-19. Although the cause of type 2 diabetes mellitus is unknown, it is believed to involve a complex array of genetic defects that affect metabolic pathways which eventually lead to hyperglycaemia. This hyperglycaemia arises from an inability of the insulin-sensitive cells to sufficiently respond to the secreted insulin, which eventually results in the inadequate secretion of insulin from pancreatic β-cells. Several treatments, utilising a variety of mechanisms, are available for type 2 diabetes mellitus. However, more medications are needed to assist with the optimal management of the different stages of the disease in patients of varying ages with the diverse combinations of other medications co-administered. Throughout modern history, some lead constituents from ancient medicinal plants have been investigated extensively and helped in developing synthetic antidiabetic drugs, such as metformin. Teucrium polium L. (Tp) is a herb that has a folk reputation for its antidiabetic potential. Previous studies indicate that Tp extracts significantly decrease blood glucose levels r and induce insulin secretion from pancreatic β-cells in vitro. Nonetheless, the constituent/s responsible for this action have not yet been elucidated. The effects appear to be, at least in part, attributable to the presence of selected flavonoids (apigenin, quercetin, and rutin). This review aims to examine the reported glucose-lowering effect of the herb, with a keen focus on insulin secretion, specifically related to type 2 diabetes mellitus. An analysis of the contribution of the key constituent flavonoids of Tp extracts will also be discussed.

scholarly journals Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

2022 ◽  
Author(s):  
Marta Garaulet ◽  
Jesus Lopez-Minguez ◽  
Hassan S Dashti ◽  
Céline Vetter ◽  
Antonio Miguel Hernández-Martínez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Elevated Concentration ◽  
Endogenous Melatonin

<strong>Objective: </strong>We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P<sub>int</sub></i><sub> </sub>AUCgluc=0.009, <i>P<sub>int</sub></i><sub> </sub>CIR=0.022, <i>P<sub>int </sub></i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>

Plasma GLP-1 response to oral and intraduodenal nutrients in health and type 2 diabetes – impact on gastric emptying

2021 ◽  
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Linda E Watson ◽  
Stijn Soenen ◽  
Richard L Young ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Breath Test ◽  
Oral Glucose ◽  
Gastric Emptying Rate ◽  
Postprandial Glycemia ◽  
Glucagon Like Peptide 1 ◽  
The Relationship ◽  
Potato Meal

Abstract Context Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying. Objective To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D. Design We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 T2D subjects; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4kcal/min) during euglycemia and hyperglycemia in 11 healthy, and 12 T2D, subjects, (b) intraduodenal fat (2kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75g oral glucose and the GLP-1 response to intraduodenal glucose (4kcal/min) in 21 subjects (9 healthy, 12 T2D). Results The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r=0.65, P=0.002). Conclusions In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients.

Pharmacophore modeling and molecular docking studies of acridines as potential DPP-IV inhibitors

2015 ◽  
Vol 93 (7) ◽  
pp. 721-729
Author(s):  
R. Abu Khalaf ◽  
Z. Jarekji ◽  
T. Al-Qirim ◽  
D. Sabbah ◽  
G. Shattat
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Inhibitory Polypeptide ◽  
Pharmacophore Modeling ◽  
Docking Studies ◽  
Glucose Levels ◽  
Dpp Iv ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Circulating Levels

Inhibition of dipeptidyl peptidase-IV (DPP-IV) prevents the inactivation of gastric inhibitory polypeptide (GIP) and glucagon-like peptide–1 (GLP-1). This increases circulating levels of active GLP-1 and GIP and stimulates insulin secretion, which results in lowering of glucose levels and improvement of the glycemic control in patients with type 2 diabetes. In this study, pharmacophore modeling and docking experiments were carried out and a series of eight novel 2-ethoxy-6,9-disubstituted acridines (13, 15, and 17a–17f) have been designed and synthesized. Then, these compounds were evaluated for their ability to inhibit DPP-IV. Most of the synthesized compounds were proven to have anti-DPP-IV activity where compound 17b displayed the best activity of 43.8% inhibition at 30 μmol/L concentration. Results of this work might be helpful for further optimization to develop more potent DPP-IV inhibitors.

Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

2014 ◽  
Vol 307 (7) ◽  
pp. R862-R868 ◽  
Author(s):  
Jennifer P. Richards ◽  
Gina L. C. Yosten ◽  
Grant R. Kolar ◽  
Cory W. Jones ◽  
Alan H. Stephenson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Tissue Oxygenation ◽  
Atp Release ◽  
Peripheral Vascular ◽  
Healthy Human ◽  
C Peptide ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Healthy Humans

ATP release from erythrocytes in response to reduced oxygen (O2) tension stimulates local vasodilation, enabling these cells to direct perfusion to areas in skeletal muscle in need of O2. Erythrocytes of humans with type 2 diabetes do not release ATP in response to low O2. Both C-peptide and insulin individually inhibit low O2-induced ATP release from healthy human erythrocytes, yet when coadministered at physiological concentrations and ratios, no inhibition is seen. Here, we determined: that 1) erythrocytes of healthy humans and humans with type 2 diabetes possess a C-peptide receptor (GPR146), 2) the combination of C-peptide and insulin at physiological ratios rescues low O2-induced ATP release from erythrocytes of humans with type 2 diabetes, 3) residual C-peptide levels reported in humans with type 2 diabetes are not adequate to rescue low O2-induced ATP release in the presence of 1 nM insulin, and 4) the effects of C-peptide and insulin are neither altered by increased glucose levels nor explained by changes in erythrocyte deformability. These results suggest that the addition of C-peptide to the treatment regimen for type 2 diabetes could have beneficial effects on tissue oxygenation, which would help to ameliorate the concomitant peripheral vascular disease.

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