INT145960

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Context Info
Confidence 0.58
First Reported 2007
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 19
Total Number 20
Disease Relevance 7.25
Pain Relevance 1.19

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

small molecule metabolic process (GLP1R) plasma membrane (GLP1R) signal transducer activity (GLP1R)
Anatomy Link Frequency
plasma 3
liver 1
proximal 1
stomach 1
GLP1R (Homo sapiens)
Pain Link Frequency Relevance Heat
substance P 6 100.00 Very High Very High Very High
bradykinin 6 100.00 Very High Very High Very High
Enkephalin 2 100.00 Very High Very High Very High
Chronic pancreatitis 58 99.68 Very High Very High Very High
agonist 119 98.24 Very High Very High Very High
abdominal pain 24 93.72 High High
adenocard 16 91.16 High High
Central nervous system 9 68.48 Quite High
tolerance 18 59.24 Quite High
potassium channel 8 14.36 Low Low
Disease Link Frequency Relevance Heat
Natriuresis 7 100.00 Very High Very High Very High
Diabetes Mellitus 719 99.72 Very High Very High Very High
Pancreatitis 87 99.68 Very High Very High Very High
Obesity 52 99.44 Very High Very High Very High
Vomiting 82 99.04 Very High Very High Very High
Diarrhoea 14 94.96 High High
Renal Failure 13 94.44 High High
Abdominal Pain 24 93.72 High High
Gastric Motility Disorder 3 92.60 High High
Sprains And Strains 5 85.60 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Also, subcutaneous injections of GLP-1 do not lead to a sufficiently high and long-lasting elevation of GLP-1 concentrations to use native GLP-1 as a practical therapeutic agent.
Positive_regulation (elevation) of GLP-1
1) Confidence 0.58 Published 2010 Journal Pediatr Nephrol Section Body Doc Link PMC2874027 Disease Relevance 0.67 Pain Relevance 0.10
After once- or twice-daily dosing they effectively inhibit DPP-4 and lead to a postprandial elevation of endogenous GLP-1 concentrations 2–3 times normal physiological levels [62, 63].
Positive_regulation (elevation) of GLP-1
2) Confidence 0.58 Published 2010 Journal Pediatr Nephrol Section Body Doc Link PMC2874027 Disease Relevance 0.21 Pain Relevance 0
Increasing GLP-1 plasma concentrations to pharmacological levels by exogenous GLP-1 application leads to a normalisation of the incretin effect with an adequate insulin response under hyperglycaemic conditions [12].


Positive_regulation (Increasing) of GLP-1 in plasma
3) Confidence 0.51 Published 2010 Journal Pediatr Nephrol Section Body Doc Link PMC2874027 Disease Relevance 0.45 Pain Relevance 0.03
Through preventing the rapid degradation of incretin hormones, DPP-4 inhibitors result in postprandial increases in levels of biologically active intact GLP-1 and reduce glucose production from the liver by inhibition of glucagon from the ?
Positive_regulation (increases) of GLP-1 in liver
4) Confidence 0.43 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2597770 Disease Relevance 0.07 Pain Relevance 0
In the past decade, the pharmacological actions of the incretin hormone glucagon-like peptide-1 (GLP-1) were utilised to develop two novel substance classes for type 2 diabetes therapy: the GLP-1 receptor agonists (or “GLP-1 mimetics”) and the dipeptidyl-peptidase-IV inhibitors (DPP-4 inhibitors or “GLP-1 enhancers”) [6].
Positive_regulation (enhancers) of GLP-1 associated with diabetes mellitus and agonist
5) Confidence 0.42 Published 2010 Journal Pediatr Nephrol Section Body Doc Link PMC2874027 Disease Relevance 0.36 Pain Relevance 0.05
Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor, as well as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent stimulator of insulin secretion.
Positive_regulation (inactivation) of GLP-1 associated with natriuresis, enkephalin, bradykinin and substance p
6) Confidence 0.42 Published 2007 Journal Acta Crystallogr. D Biol. Crystallogr. Section Abstract Doc Link 17704566 Disease Relevance 0.25 Pain Relevance 0.20
GLP-1 receptor activation most likely influences the activity of the sodium-proton exchanger 3 (NHE3 = natrium-proton [H+] exchanger 3) located in the brush border membrane of the proximal tubular cells by activation pathways involving cAMP (cyclic adenosine mono-phosphate) and protein kinase A [100].
Positive_regulation (activation) of GLP-1 receptor in proximal associated with adenocard
7) Confidence 0.39 Published 2010 Journal Pediatr Nephrol Section Body Doc Link PMC2874027 Disease Relevance 0.66 Pain Relevance 0.11
Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor, as well as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent stimulator of insulin secretion.
Positive_regulation (inactivation) of glucagon-like peptide 1 associated with natriuresis, enkephalin, bradykinin and substance p
8) Confidence 0.37 Published 2007 Journal Acta Crystallogr. D Biol. Crystallogr. Section Abstract Doc Link 17704566 Disease Relevance 0.25 Pain Relevance 0.20
Saxagliptin (Onglyza®; Bristol-Myers Squibb) is also a potent, selective DPP-4 inhibitor specifically designed for extended inhibition of the DPP-4 enzyme causing increased endogenous GLP-1 concentration, and is now approved by the FDA.


Positive_regulation (increased) of GLP-1
9) Confidence 0.36 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2878957 Disease Relevance 0.27 Pain Relevance 0.06
Saxagliptin, a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor specifically designed for extended inhibition of the DPP-4 enzyme, causes increased endogenous GLP-1 concentration.
Positive_regulation (increased) of GLP-1
10) Confidence 0.36 Published 2010 Journal Therapeutics and Clinical Risk Management Section Abstract Doc Link PMC2878957 Disease Relevance 0.26 Pain Relevance 0
It could be demonstrated that DPP-4 inhibition increases circulating levels of GLP-1 in experimental animals and that the insulinotropic action of exogenously administered GLP-1 is intensified by DPP-4 inhibition (Holst and Deacon 1998).
Positive_regulation (increases) of GLP-1
11) Confidence 0.31 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2597770 Disease Relevance 0.20 Pain Relevance 0
DPP-4 inhibition increases not only prandial but also fasting levels of active GLP-1 and results in an overall increase in GLP-1 levels with maintenance of circadian rhythm throughout the day.
Positive_regulation (increase) of GLP-1
12) Confidence 0.29 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2597770 Disease Relevance 0.13 Pain Relevance 0
As a result of DPP-4 activity, intact, biologically active GLP-1 represents only 10% to 20% of total plasma GLP-1 (Deacon et al 1995).
Positive_regulation (result) of GLP-1 in plasma
13) Confidence 0.29 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2597770 Disease Relevance 0.30 Pain Relevance 0
Inhibition of DPP-4 activity by 80% results in a 2- to 3-fold increase in active GLP-1 levels, and is the level of inhibition at which near maximal glucose lowering is seen.
Positive_regulation (increase) of GLP-1
14) Confidence 0.17 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2597758 Disease Relevance 0.13 Pain Relevance 0.03
Administration of metformin to obese subjects was also found to increase levels of active GLP-1 after a glucose load: this phenomenon appears to occur through mechanisms other than DPP-4 inhibition, and may instead be due to direct stimulation of GLP-1 secretion or a reduction in DPP-4 secretion (Mannucci et al 2001; Lenhard et al 2004).
Positive_regulation (increase) of GLP-1 associated with obesity
15) Confidence 0.17 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2597758 Disease Relevance 0.30 Pain Relevance 0.05
GLP-1 levels after DPP-4 inhibition are increased, resulting in stimulation of insulin secretion and suppression of glucagon secretion in a fashion which is glucose-dependent (ie, glucose-appropriate).
Positive_regulation (increased) of GLP-1
16) Confidence 0.17 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2597758 Disease Relevance 0.12 Pain Relevance 0
This was not unexpected because the increased levels of active GLP-1 and GIP observed with the use of DPP-4 inhibitors remain within a physiologic range [3].
Positive_regulation (levels) of GLP-1
17) Confidence 0.10 Published 2008 Journal BMC Endocr Disord Section Body Doc Link PMC2605739 Disease Relevance 0.62 Pain Relevance 0
This was not unexpected because the increased levels of active GLP-1 and GIP observed with the use of DPP-4 inhibitors remain within a physiologic range [3].
Positive_regulation (increased) of GLP-1
18) Confidence 0.10 Published 2008 Journal BMC Endocr Disord Section Body Doc Link PMC2605739 Disease Relevance 0.63 Pain Relevance 0
Since sitagliptin increases intact GLP-1 and GIP levels by 2- to 3-fold [2,18], certain GI adverse experiences were pre-specified for statistical analysis (including diarrhea, nausea, vomiting and abdominal pain [including upper and lower abdominal pain and abdominal/stomach discomfort]) in the sitagliptin development program.
Positive_regulation (increases) of GLP-1 in stomach associated with abdominal pain, diarrhoea and vomiting
19) Confidence 0.07 Published 2008 Journal BMC Endocr Disord Section Body Doc Link PMC2605739 Disease Relevance 0.83 Pain Relevance 0.19
Incretins (mainly GLP-1 (glucagon like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide)) are insulinotropic intestinal peptide hormones released in response to simple carbohydrates and lipids, that cause an increase in the amount of insulin released from the beta cells in the pancreas.52 PES has been shown to restore the GIP response in CP patients.53 An increase in GLP-1 has also been described following PES.54 The increase in incretin levels was accompanied by an increase in plasma insulin and c-peptide levels, but without a significant lowering of plasma glucose levels (Figure 2).
Positive_regulation (increase) of GLP-1 in plasma associated with chronic pancreatitis
20) Confidence 0.02 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2710383 Disease Relevance 0.57 Pain Relevance 0.18

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