Effects of C-Peptide and Glucagon-Like Peptide-1 on Diabetic Male Albino Rats with and without Antioxidants = تأثیر سي - بیبتید و الجلوكاجون شبیه بیبتید - ۱على ذكور الفئران المصابة بداء السكري مع و بدون مضادات الأكسدة

2015 ◽  
Vol 44 (2-3) ◽  
pp. 179-190
Author(s):  
Mohammad Mohammad El-Shawwa ◽  
Saad Kamal Taha ◽  
Hamed Mohamed Osman
2016 ◽  
Vol 310 (1) ◽  
pp. G43-G51 ◽  
Author(s):  
Simon Veedfald ◽  
Astrid Plamboeck ◽  
Carolyn F. Deacon ◽  
Bolette Hartmann ◽  
Filip K. Knop ◽  
...  

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m2; HbA1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka “chew and spit”) with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg−1·min−1 for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were −10.7 ± 1.1 vs. −4.0 ± 1.1 and −4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.


2005 ◽  
Vol 186 (2) ◽  
pp. 343-352 ◽  
Author(s):  
L Bai ◽  
G Meredith ◽  
B E Tuch

Embryonic stem cells (ESCs) can be differentiated into insulin-producing cells by a five-stage procedure involving altering culture conditions and addition of nicotinamide. The amounts of insulin in these cells are lower than those found in pancreatic β cells. Glucagon-like peptide-1 (GLP-1) induces the differentiation of β cells from ductal progenitor cells. We examined the possibility of GLP-1, and its long-acting agonist exendin-4, enhancing the differentiation of insulin-producing cells from mouse ESCs (mESCs). A five-stage culturing strategy starting with embryoid bodies (EBs) was used in this study. mRNA for pancreatic duodenal homeobox gene 1 (PDX-1) and neurogenic differentiation (NeuroD) was detected from stage 1, hepatocyte nuclear factor 3 beta (HNF3β) and insulin 2 from stage 2, Ngn3 and glucose transporter 2 (GLUT2) from stage 3, and insulin 1 and other β-cell markers, at stages 4–5. Cells at stage 5 secreted C-peptide, being 0.68 ± 0.01 pmol/106 cells per 2 days, and had an immunoreactive insulin content of 13.5 ± 0.7 pmol/106 cells. Addition of GLP-1 (100 nM) and nicotinamide (10 mM) at stage 5 resulted in a 50% and 48% increase in insulin content and C-peptide secretion respectively compared with nicotinamide alone. Glucose-induced insulin secretion was enhanced 4-fold by addition of both growth factors. The GLP-1 receptor was present at all five stages of the culture. Addition of exendin-4 to cells at stage 2 resulted in a 4.9-fold increase in expression of the gene for insulin 1 and a 2-fold increase in insulin content compared with the effect of nicotinamide alone at stage 5. It is concluded that both GLP-1 and exendin-4 enhance the level of expression of insulin in glucose-responsive insulin-producing cells derived from the R1 mESC line.


2018 ◽  
Vol 314 (5) ◽  
pp. R639-R646 ◽  
Author(s):  
Andrea Tura ◽  
Roberto Bizzotto ◽  
Yuchiro Yamada ◽  
Yutaka Seino ◽  
Giovanni Pacini ◽  
...  

To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO ( n = 31) and wild-type (WT) C57BL6J mice ( n = 45) were intravenously injected with d-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10−3 1/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10−3 l/min in DIRKO mice vs. 0.54 ± 0.03 10−3 1/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion ( P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.


Author(s):  
Kathleen M. Antony ◽  
Mona Romezi ◽  
Kourtnee Lindgren ◽  
Kristen B. Mitchell ◽  
Susan F. Venable ◽  
...  

Abstract Objective The purpose of this study was to evaluate the independent contribution of maternal obesity and gestational weight gain (GWG) in excess of the Institute of Medicine's guidelines on levels of maternal serum inflammatory and metabolic measures. Study Design Banked maternal serum samples from 120 subjects with documented prepregnancy or first trimester body mass index (BMI) were utilized for analyte analyses. Validated, BMI-specific formulas were utilized to categorize GWG as either insufficient, at goal or excess based on the Institute of Medicine guidelines with gestational age adjustments. Serum was analyzed for known inflammatory or metabolic pathway intermediates using the Luminex xMap system with the MILLIPLEX Human Metabolic Hormone Magnetic Bead Panel. Measured analytes included interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α and metabolic markers amylin, c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, pancreatic polypeptide, and peptide YY. Kruskal–Wallis ANOVA and Pearson's correlation coefficients were calculated for each marker. Results C-peptide, insulin, and leptin all varied significantly with both obesity and GWG while glucagon-like peptide-1 varied by BMI but not GWG. These analytes covaried with other metabolic analytes, but not with inflammatory analytes. Conclusion Maternal metabolic biomarkers at delivery vary significantly with both obesity and GWG. Taken together, these findings suggest that GWG (with and without comorbid obesity) is an important mediator of measurable metabolites in pregnancy but is not necessarily accompanied by inflammatory measures in serum. These findings are consistent with GWG being an independent risk factor for metabolic disturbances during pregnancy.


2016 ◽  
Vol 56 (3) ◽  
pp. 1053-1062 ◽  
Author(s):  
Meena Shah ◽  
Brian Franklin ◽  
Beverley Adams-Huet ◽  
Joel Mitchell ◽  
Brooke Bouza ◽  
...  

2021 ◽  
pp. 1-29
Author(s):  
Marina V. Geraldi ◽  
Cínthia B. B. Cazarin ◽  
Marcelo Cristianini ◽  
Ana C. Vasques ◽  
Bruno Geloneze ◽  
...  

Abstract Jabuticaba is a Brazilian berry rich in polyphenols, which may exert beneficial effects on metabolic diseases. This randomized crossover study aimed to determine the effects of jabuticaba juice (250 ml in a portion) on postprandial response. Sixteen healthy subjects (11 women; 5 men; 28.4 ± 3.8 years old; body mass index (BMI) 21.7 ± 2.3 kg m−2) consumed two test products after fasting overnight in a randomized controlled crossover design. Each test product portion had a similar composition of sugar components: 250 mL water with glucose, fructose, colored with artificial non-caloric food colorings (placebo); and 250 mL of jabuticaba juice. Beverages were administered immediately before a carbohydrate meal. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min after each test product to analyze the concentrations of glucose, insulin, C-peptide, antioxidant capacity, plasma glucagon-like peptide-1 (GLP-1), and appetite sensations. Compared to the placebo, the intake of jabuticaba juice resulted in a higher GLP-1 response as the area under the curve (AUC) and peaking at 60 min. Jabuticaba juice also resulted in higher antioxidant capacity. Postprandial glucose, insulin, C-peptide levels, and appetite sensations were not significantly different between tests. In conclusion, 250 mL of jabuticaba juice before a carbohydrate meal was able to improve the antioxidant status and GLP-1 concentrations in healthy subjects.


2006 ◽  
Vol 290 (6) ◽  
pp. E1118-E1123 ◽  
Author(s):  
Juris J. Meier ◽  
Arnica Gethmann ◽  
Michael A. Nauck ◽  
Oliver Götze ◽  
Frank Schmitz ◽  
...  

Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7–36) amide is degraded to the metabolite GLP-1-(9–36) amide. The effects of GLP-1-(9–36) amide in humans are less well characterized. Fourteen healthy volunteers were studied with intravenous infusion of GLP-1-(7–36) amide, GLP-1-(9–36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements. Administration of GLP-1-(7–36) amide and GLP-1-(9–36) amide significantly raised total GLP-1 plasma levels. Plasma concentrations of intact GLP-1 increased to 21 ± 5 pmol/l during the infusion of GLP-1-(7–36) amide but remained unchanged during GLP-1-(9–36) amide infusion [5 ± 3 pmol/l; P < 0.001 vs. GLP-1-(7–36) amide administration]. GLP-1-(7–36) amide reduced fasting and postprandial glucose concentrations ( P < 0.001) and delayed gastric emptying ( P < 0.001). The GLP-1 metabolite had no influence on insulin or C-peptide concentrations. Glucagon levels were lowered by GLP-1-(7–36) amide but not by GLP-1-(9–36) amide. However, the postprandial rise in glycemia was reduced significantly (by ∼6 mg/dl) by GLP-1-(9–36) amide ( P < 0.05). In contrast, gastric emptying was completely unaffected by the GLP-1 metabolite. The GLP-1 metabolite lowers postprandial glycemia independently of changes in insulin and glucagon secretion or in the rate of gastric emptying. Most likely, this is because of direct effects on glucose disposal. However, the glucose-lowering potential of GLP-1-(9–36) amide appears to be small compared with that of intact GLP-1-(7–36) amide.


2007 ◽  
Vol 293 (3) ◽  
pp. E849-E856 ◽  
Author(s):  
Juris J. Meier ◽  
Jens J. Holst ◽  
Wolfgang E. Schmidt ◽  
Michael A. Nauck

Changes in hepatic insulin clearance can occur after oral glucose or meal ingestion. This has been attributed to the secretion and action of gastric inhibitory polypeptide (GIP) and glucagon-like peptide (GLP)−1. Given the recent availability of drugs based on incretin hormones, such clearance effects may be important for the future treatment of type 2 diabetes. Therefore, we determined insulin clearance in response to endogenously secreted and exogenously administered GIP and GLP-1. Insulin clearance was estimated from the molar C-peptide-to-insulin ratio calculated at basal conditions and from the respective areas under the curve after glucose, GIP, or GLP-1 administration. Oral glucose administration led to an ∼60% reduction in the C-peptide-to-insulin ratio ( P < 0.0001), whereas intravenous glucose administration had no effect ( P = 0.09). The endogenous secretion of GIP or GLP-1 was unrelated to the changes in insulin clearance. The C-peptide-to-insulin ratio was unchanged after the intravenous administration of GIP or GLP-1 in the fasting state ( P = 0.27 and P = 0.35, respectively). Likewise, infusing GLP-1 during a meal course did not alter insulin clearance ( P = 0.87). An inverse nonlinear relationship was found between the C-peptide-to-insulin ratio and the integrated insulin levels after oral and during intravenous glucose administration. Insulin clearance is reduced by oral but not by intravenous glucose administration. Neither GIP nor GLP-1 has significant effects on insulin extraction. An inverse relationship between insulin concentrations and insulin clearance suggests that the secretion of insulin itself determines the rate of hepatic insulin clearance.


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