Millipore Sigma Vibrant Logo
 

eglp-35k


67 Results Advanced Search  
Showing
Products (3)
Documents (57)
Site Content (7)

Narrow Your Results Use the filters below to refine your search

Document Type

  • (53)
  • (2)
  • (1)
  • (1)
Can't Find What You're Looking For?
Contact Customer Service

 

  • Expression of proglucagon and proglucagon-derived peptide hormone receptor genes in the chicken. 18299131

    To better understand how the proglucagon system functions in birds, we utilized a molecular cloning strategy to sequence and characterize the chicken proglucagon gene that encodes glucagon, glucagon-like peptide (GLP)-1 and GLP-2. This gene has seven exons and six introns with evidence for an additional (alternate) first exon and two promoter regions. We identified two distinct classes of proglucagon mRNA transcripts (PGA and PGB) produced by alternative splicing at their 3'-ends. These were co-expressed in all tissues examined with pancreas and proventriculus showing the highest levels of each. Although both mRNA classes contained coding sequence for glucagon and GLP-1, class A mRNA lacked that portion of the coding region (CDS) containing GLP-2; whereas, class B mRNA had a larger CDS that included GLP-2. Both classes of mRNA transcripts exhibited two variants, each with a different 5'-end arising from alternate promoter and alternate first exon usage. Fasting and refeeding had no effect on proglucagon mRNA expression despite significant changes in plasma glucagon levels. To investigate potential differences in proglucagon precursor processing among tissues, mRNA expression for two prohormone convertase (PC) genes was analyzed. PC2 mRNA was predominantly expressed in pancreas and proventriculus, whereas PC1/3 mRNA was more highly expressed in duodenum and brain. We also determined mRNA expression of the specific receptor genes for glucagon, GLP-1 and GLP-2 to help define major sites of hormone action. Glucagon receptor mRNA was most highly expressed in liver and abdominal fat, whereas GLP-1 and GLP-2 receptor genes were highly expressed in the gastrointestinal tract, brain, pancreas and abdominal fat. These results offer new insights into structure and function of the chicken proglucagon gene, processing of the precursor proteins produced from it and potential activity sites for proglucagon-derived peptide hormones mediated by their cognate receptors.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Engineered glucagon-like peptide-1-producing hepatocytes lower plasma glucose levels in mice. 19190262

    Glucagon-like peptide (GLP)-1 is an incretin hormone with well-characterized antidiabetic properties, including glucose-dependent stimulation of insulin secretion and enhancement of beta-cell mass. GLP-1 agonists have recently been developed and are now in clinical use for the treatment of type 2 diabetes. Rapid degradation of GLP-1 by enzymes including dipeptidyl-peptidase (DPP)-IV and neutral endopeptidase (NEP) 24.11, along with renal clearance, contribute to a short biological half-life, necessitating frequent injections to maintain therapeutic efficacy. Gene therapy may represent a promising alternative approach for achieving long-term increases in endogenous release of GLP-1. We have developed a novel strategy for glucose-regulated production of GLP-1 in hepatocytes by expressing a DPP-IV-resistant GLP-1 peptide in hepatocytes under control of the liver-type pyruvate kinase promoter. Adenoviral delivery of this construct to hepatocytes in vitro resulted in production and secretion of bioactive GLP-1 as measured by a luciferase-based bioassay developed to detect the NH(2)-terminally modified GLP-1 peptide engineered for this study. Transplantation of encapsulated hepatocytes into CD-1 mice resulted in an increase in plasma GLP-1 levels that was accompanied by a significant reduction in fasting plasma glucose levels. The results from this study demonstrate that a gene therapy approach designed to induce GLP-1 production in hepatocytes may represent a novel strategy for long-term secretion of bioactive GLP-1 for the treatment of type 2 diabetes.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Elevated glucagon-like peptide-1-(7-36)-amide, but not glucose, associated with hyperinsulinemic compensation for fat feeding. 12414891

    We previously developed a canine model of central obesity and insulin resistance by supplementing the normal chow diet with 2 g cooked bacon grease/kg body weight. Dogs fed this fatty diet maintained glucose tolerance with compensatory hyperinsulinemia. The signal(s) responsible for this up-regulation of plasma insulin is unknown. We hypothesized that meal-derived factors such as glucose, fatty acids, or incretin hormones may signal beta-cell compensation in the fat-fed dog. We fed the same fat-supplemented diet for 12 wk to six dogs and compared metabolic responses with seven control dogs fed a normal diet. Fasting and stimulated fatty acid and glucose-dependent insulinotropic peptide concentrations were not increased by fat feeding, whereas glucose was paradoxically decreased, ruling out those three factors as signals for compensatory hyperinsulinemia. Fasting plasma glucagon-like peptide-1 (GLP-1) concentration was 2.5-fold higher in the fat-fed animals, compared with controls, and 3.4-fold higher after a mixed meal. Additionally, expression of the GLP-1 receptor in whole pancreas was increased 2.3-fold in the fat-fed dogs. The increase in both circulating GLP-1 and its target receptor may have increased beta-cell responsiveness to lower glucose. Glucose is not the primary cause of hyperinsulinemia in the fat-fed dog. Corequisite meal-related signals may be permissive for development of hyperinsulinemia.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Racial disparity in glucagon-like peptide 1 and inflammation markers among severely obese adolescents. 18184905

    OBJECTIVE: Compared with Caucasians, obese African-American adolescents have a higher risk for type 2 diabetes. Subclinical inflammation and reduced glucagon-like peptide 1 (GLP-1) concentration are linked to the pathogenesis of the disease. We determined the relationship between insulin resistance, beta-cell activity, and subclinical inflammation with GLP-1 concentrations and whether racial disparities in GLP-1 response were present in 49 obese adolescents (14 +/- 3 years; 76% African American; 71% female). RESEARCH DESIGN AND METHODS: Subjects underwent physical examination and an oral glucose tolerance test. We measured levels of high-sensitivity CRP (CRP(hs)), fibrinogen, glucose, GLP-1(total), GLP-1(active), and insulin. Insulin and glucose area under the curve (AUC), insulinogenic index (DeltaI30/DeltaG30), and composite insulin sensitivity index (CISI) were computed. Subjects were categorized by race and as inflammation positive (INF+) if CRP(hs) or fibrinogen were elevated. RESULTS: No racial differences were seen in mean or relative BMI. Thirty-five percent of subjects had altered fasting or 2-h glucose levels (African American vs. Caucasian, NS), and 75% were INF+ (African American vs. Caucasian, P = 0.046). Glucose and insulin, CISI, and DeltaI30/DeltaG30 values were similar; African Americans had lower GLP-1(total) AUC (P = 0.01), GLP-1(active) at 15 min (P = 0.03), and GLP-1(active) AUC (P = 0.06) and higher fibrinogen (P = 0.01) and CRP(hs) (NS) compared with Caucasians. CONCLUSIONS: African Americans exhibited lower GLP-1 concentrations and increased inflammatory response. Both mechanisms may act synergistically to enhance the predisposition of obese African Americans to type 2 diabetes. Our findings might be relevant to effective deployment of emerging GLP-1-based treatments across ethnicities.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Effective and safe gene-based delivery of GLP-1 using chitosanplasmid-DNA therapeutic nanocomplexes in an animal model of type 2 diabetes. 21412280

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates blood glucose level post-prandially. It has been proposed that GLP-1 can be used in type 2 diabetes (T2D) mellitus treatment because of its insulinotropic action. Despite its remarkable advantages, GLP-1 suffers the disadvantage of an extremely short half-life owing to its degradation by the dipeptidyl peptidase IV protease. One way of overcoming this drawback is GLP-1 gene delivery. Here we show effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes (TNCs) in Zucker diabetic fatty (ZDF) animal model of T2D. The expression plasmid fused the GLP-1 gene to a Furin cleavage site was driven by a cytomegalovirus promoter/enhancer. TNCs were prepared by mixing this plasmid with chitosans of specific molecular weight (MW), degree of deacetylation (DDA) and ratio of chitosan amine to DNA phosphate (N:P ratio). Animals injected with the TNC chitosan 92-10-5 (DDA-MW-N:P) showed GLP-1 plasma levels of about fivefold higher than that in non-treated animals and the insulinotropic effect of recombinant GLP-1 was shown by a threefold increase in plasma insulin concentration when compared with untreated animals. Intraperitoneal glucose tolerance tests revealed an efficacious decrease of blood glucose compared with controls for up to 24 days after treatment, where injections of this formulation allowed near-normalization of blood glucose level. TNCs composed of specific chitosans and GLP-1-expressing plasmid constructs showed an impressive ability to harness the profound therapeutic potential of GLP-1 for the treatment of T2D mellitus.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. 18065574

    BACKGROUND: It is unclear whether energy-containing drinks, especially those sweetened with high-fructose corn syrup (HFCS), promote positive energy balance and thereby play a role in the development of obesity. OBJECTIVE: The objective was to examine the satiating effects of HFCS and sucrose in comparison with milk and a diet drink. DESIGN: The effects of four 800-mL drinks [corrected] containing no energy or 1.5 MJ from sucrose, HFCS, or milk on satiety were assessed, first in 15 men and 15 women with a mean (+/-SD) body mass index (BMI; in kg/m(2)) of 22.1 +/- 1.9 according to visual analogue scales (VAS) and blood variables and second in 20 men and 20 women (BMI: 22.4 +/- 2.1) according to ingestion of a standardized ad libitum meal (granola cereal + yogurt, 10.1 kJ/g). RESULTS: Fifty minutes after consumption of the 1.5-MJ preload drinks containing sucrose, HFCS, or milk, 170%-mm VAS changes in satiety were observed. Glucagon-like peptide 1 (GLP-1) (P 0.001) and ghrelin (P 0.05) concentrations changed accordingly. Compensatory energy intake did not differ significantly between the 3 preloads and ranged from 30% to 45%. Energy intake compensations were related to satiety (r = 0.35, P 0.05). No differences were observed between the effects of the sucrose- and HFCS-containing drinks on changes in VAS and on insulin, glucose, GLP-1, and ghrelin concentrations. Changes in appetite VAS ratings were a function of changes in GLP-1, ghrelin, insulin, and glucose concentrations. CONCLUSION: Energy balance consequences of HFCS-sweetened soft drinks are not different from those of other isoenergetic drinks, eg, a sucrose-drink or milk.
    Document Type:
    Reference
    Product Catalog Number:
    EGLP-35K
    Product Catalog Name:
    Glucagon Like Peptide-1 (Active) ELISA

  • Acute effects of breakfasts containing alpha-lactalbumin, or gelatin with or without added tryptophan, on hunger, 'satiety' hormones and amino acid profiles. 19017422

    Proteins are the most satiating macronutrients. Tryptophan (TRP) may contribute to the satiating effect, as it serves as a precursor for the anorexigenic neurotransmitter serotonin. To address the role of TRP in the satiating properties of dietary protein, we compared three different breakfasts, containing either alpha-lactalbumin (high in TRP), gelatin (low in TRP) or gelatin with added TRP (gelatin+TRP, high in TRP), on appetite. Twenty-four subjects (22-29 kg/m2; aged 19-37 years) received a subject-specific breakfast at t = 0 with 10, 55 and 35 % energy from protein, carbohydrate and fat respectively in a randomised, single-blind design. Hunger, glucagon-like peptide (GLP)-1, ghrelin, amino acid concentrations and energy intake during a subsequent lunch were determined. Suppression of hunger was stronger 240 min after the breakfast with alpha-lactalbumin compared with gelatin and gelatin+TRP. Total plasma amino acid concentrations were lower with alpha-lactalbumin compared with gelatin with or without TRP (from t = 180-240 min). TRP concentrations were higher after alpha-lactalbumin than after gelatin with or without TRP from t = 0-100 min, whereas from t = 100-240 min, TRP concentrations were lower after gelatin than after alpha-lactalbumin and gelatin+TRP. The plasma ratio of TRP to other large neutral amino acids (LNAA) was, only at t = 100 min, lower after gelatin+TRP than after the other breakfasts. Plasma amino acid responses, TRP concentrations and TRP:LNAA ratios were not correlated with hunger. GLP-1 and ghrelin concentrations were similar for all diets. Energy intake during a subsequent lunch was similar for all diets. Summarised, an alpha-lactalbumin breakfast suppresses hunger more than a gelatin or gelatin+TRP breakfast. This cannot be explained by (possible) differences found in TRP concentrations and TRP:LNAA ratios in the breakfasts and in plasma, as well as in circulating total amino acids, GLP-1 and ghrelin.
    Document Type:
    Reference
    Product Catalog Number:
    EGLP-35K
    Product Catalog Name:
    Glucagon Like Peptide-1 (Active) ELISA

  • Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers. 22696033

    Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are secreted from enteroendocrine L cells in response to numerous stimuli, including bile salts. Both have multiple effects that are potentially useful in treating diabetes and obesity. L cell number and hormone content in the intestine are highest in the rectum in humans. We investigated the effects of intrarectal sodium taurocholate on plasma GLP-1, PYY, insulin and glucose concentrations, and on food intake of a subsequent meal.
    Document Type:
    Reference
    Product Catalog Number:
    EGLP-35K
    Product Catalog Name:
    Glucagon Like Peptide-1 (Active) ELISA

  • PPARβ/δ Activation Induces Enteroendocrine L Cell GLP-1 Production. 21300064

    BACKGROUND & AIMS: Glucagon-like peptide (GLP)-1, an intestinal incretin produced by L cells through proglucagon processing, is secreted after nutrient ingestion and acts on endocrine pancreas beta cells to enhance insulin secretion. Peroxisome proliferator-activated receptor (PPAR) β/δ is a nuclear receptor that improves glucose homeostasis and pancreas islet function in diabetic animal models. Here, we investigated whether PPARβ/δ activation regulates L cell GLP-1 production.METHODS: Proglucagon regulation and GLP-1 release were evaluated in murine GLUTag and human NCI-H716 L cells and in vivo using wild-type, PPARβ/δ-null, and ob/ob C57Bl/6 mice treated with the PPARβ/δ synthetic agonists GW501516 or GW0742.RESULTS: PPARβ/δ activation increased proglucagon expression and enhanced glucose- and bile acid-induced GLP-1 release by intestinal L cells in vitro and ex vivo in human jejunum. In vivo treatment with GW0742 increased proglucagon messenger RNA levels in the small intestine in wild-type but not in PPARβ/δ-deficient mice. Treatment of wild-type and ob/ob mice with GW501516 enhanced the increase in plasma GLP-1 level after an oral glucose load and improved glucose tolerance. Concomitantly, proglucagon and GLP-1 receptor messenger RNA levels increased in the small intestine and pancreas, respectively. Finally, PPARβ/δ agonists activate the proglucagon gene transcription by interfering with the β-catenin/TCF-4 pathway.CONCLUSIONS: Our data show that PPARβ/δ activation potentiates GLP-1 production by the small intestine. Pharmacologic targeting of PPARβ/δ is a promising approach in the treatment of patients with type 2 diabetes mellitus, especially in combination with dipeptidyl peptidase IV inhibitors.Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Document Type:
    Reference
    Product Catalog Number:
    EGLP-35K
    Product Catalog Name:
    Glucagon Like Peptide-1 (Active) ELISA

  • Effects of oral fat perception by modified sham feeding on energy expenditure, hormones and appetite profile in the postprandial state. 18814804

    Previously, we have shown that satiety and metabolites increased after high-fat modified sham feeding (MSF). We assessed possible metabolic effects due to oral stimulation with a high-fat sham-fed 'meal', in comparison with a high-fat fed meal and with water, in the postprandial state. Fourteen healthy women (aged 18-40 years; BMI 22.5 (SD 3) kg/m2) were fed in energy balance during 4 d with a 50 % energy as carbohydrate, 15 % energy as protein and 35 % energy as fat menu. On day 4, subjects were given one out of three test lunches, 5 h after a high-fat breakfast, in random order: a high-fat MSF lunch, water (W) or the same lunch to be eaten (E), during their 36 h stay in the respiration chamber, where substrate oxidation, 24 h energy expenditure (EE) and appetite profile were measured. Oral fat stimulation by MSF increased EE (W 6.3 (SD 0.8) v. MSF 6.9 (SD 1.0) kJ/min and E 6.8 (SD 0.7) kJ/min; P < 0.04) for 1 h, increased plasma insulin concentrations (t = 15; W 10.0 (SD 3.4) v. MSF 13.2 (SD 4.0) v. E 22.3 (SD 3.3) units/l; P < 0.0001), attenuated changes in plasma NEFA concentrations (t = 15, W 432 (SD 108) v. MSF 418 (SD 146) v. E 282 (SD 72) micromol/l; P < 0.0001), plasma TAG concentrations (t = 60; W 1092 (SD 548) v. MSF 1116 (SD 493) micromol/l and E 1350 (SD 352) micromol/l; P < 0.02) and plasma glycerol concentrations (t = 15, W 87 (SD 29) v. MSF 74 (SD 34) micromol/l and E 67 (SD 18) micromol/l; P < 0.03). Over a longer period of time, MSF had no effects on substrate oxidation, diet-induced thermogenesis or total EE. In addition to the previously observed metabolic effects of oral stimulation with fat, EE is stimulated up to 1 h after the MSF meal.
    Document Type:
    Reference
    Product Catalog Number:
    EGLP-35K
    Product Catalog Name:
    Glucagon Like Peptide-1 (Active) ELISA