CIDeRplusGeneral Information:
| Id: | 5,783 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
| Mammalia | |
| review | |
| Reference: | Rutter GA et al.(2015) Pancreatic beta-cell identity, glucose sensing and the control of insulin secretion Biochem. J. 466: 203-218 [PMID: 25697093] |
Interaction Information:
| Comment | Glucose is the most important physiological secretagogue for insulin. The beta-cell is thus poised to convert small fluctuations in blood glucose concentration (typically from 4.5 to 8 mM in man) into large changes in insulin secretion within minutes. |
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Formal Description Interaction-ID: 54542 |
drug/chemical compound increases_activity of |
| Comment | Within beta-cells, newly synthesized insulin is first produced as the prohormone proinsulin, and converted into mature insulin through the action of prohormone convertases (PC1, PC2, encoded by Pcsk1 and Pcsk2, respectively) during trafficking through the secretory pathway. |
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Formal Description Interaction-ID: 54543 |
gene/protein increases_activity of process |
| Drugbank entries | Show/Hide entries for PCSK1 |
| Comment | Within beta-cells, newly synthesized insulin is first produced as the prohormone proinsulin, and converted into mature insulin through the action of prohormone convertases (PC1, PC2, encoded by Pcsk1 and Pcsk2, respectively) during trafficking through the secretory pathway. |
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Formal Description Interaction-ID: 54544 |
gene/protein increases_activity of process |
| Drugbank entries | Show/Hide entries for PCSK2 |
| Comment | Within beta-cells, newly synthesized insulin is first produced as the prohormone proinsulin, and converted into mature insulin through the action of prohormone convertases (PC1, PC2, encoded by Pcsk1 and Pcsk2, respectively) during trafficking through the secretory pathway. |
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Formal Description Interaction-ID: 54545 |
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| Drugbank entries | Show/Hide entries for PCSK1 |
| Comment | Within beta-cells, newly synthesized insulin is first produced as the prohormone proinsulin, and converted into mature insulin through the action of prohormone convertases (PC1, PC2, encoded by Pcsk1 and Pcsk2, respectively) during trafficking through the secretory pathway. |
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Formal Description Interaction-ID: 54546 |
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| Drugbank entries | Show/Hide entries for PCSK2 |
| Comment | Active insulin is stored in dense core secretory granules (5‚Äď10000 per cell), each containing 300000 or more molecules of insulin. The tightly-regulated release of only a fraction of the granules through exocytosis (2 % per hour at maximal glucose concentrations) is sufficient to achieve regulation of blood glucose levels within the above narrow physiological range. This tight regulation is important not only to prevent hyperglycemia, but equally to suppress the potentially lethal hypoglycemia which would accompany over-secretion of insulin. |
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Formal Description Interaction-ID: 54548 |
process increases_activity of |
| Comment | Central to glucose sensing by beta-cells is the stimulation of glycolytic and oxidative metabolism of the sugar, ultimately causing enhanced mitochondrial ATP synthesis. Thus, flux through alternative pathways including the pentose phosphate shunt is usually small, though it may be increased under some circumstances. Increases in total, as well as free cytosolic mitochondrial matrix and sub-plasma membrane ATP/ADP ratios then lead to the closure of ATP-sensitive K + (KATP ) channels. The unbalanced influx of positively charged ions, notably Na + , then leads to plasma membrane depolarization, the firing of action potentials and the opening of voltage-gated Ca2 + channels. This, in turn, prompts the activation of secretory granule-associated small N- ethylmaleimide-sensitive factor receptor (SNARE) proteins and granule fusion with the plasma membrane. Highly localized changes in free Ca2 +, for example at the inner surface of the plasma membrane, at the mouth of voltage-gated calcium channels, and at the surface of secretory granules, are also believed to be important in controlling this process. Calcium release from intracellular organelles including the ER (endoplasmic reticulum) and Golgi [mediated via IP3 (inositol 1,4,5-trisphosphate)] as well as secretory granules and other acidic stores including lysosomes (via the generation of nicotinic acid‚Äďadenine dinucleotide phosphate, NAADP), may also be involved. Although this is a contested area this description summarizes the essentials of the ‚Äėcanonical‚Äô pathway for glucose-stimulated insulin secretion. |
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Formal Description Interaction-ID: 54549 |
process increases_quantity of drug/chemical compound |
| Comment | Central to glucose sensing by beta-cells is the stimulation of glycolytic and oxidative metabolism of the sugar, ultimately causing enhanced mitochondrial ATP synthesis. Thus, flux through alternative pathways including the pentose phosphate shunt is usually small, though it may be increased under some circumstances. Increases in total, as well as free cytosolic mitochondrial matrix and sub-plasma membrane ATP/ADP ratios then lead to the closure of ATP-sensitive K + (KATP ) channels. The unbalanced influx of positively charged ions, notably Na + , then leads to plasma membrane depolarization, the firing of action potentials and the opening of voltage-gated Ca2 + channels. This, in turn, prompts the activation of secretory granule-associated small N- ethylmaleimide-sensitive factor receptor (SNARE) proteins and granule fusion with the plasma membrane. Highly localized changes in free Ca2 +, for example at the inner surface of the plasma membrane, at the mouth of voltage-gated calcium channels, and at the surface of secretory granules, are also believed to be important in controlling this process. Calcium release from intracellular organelles including the ER (endoplasmic reticulum) and Golgi [mediated via IP3 (inositol 1,4,5-trisphosphate)] as well as secretory granules and other acidic stores including lysosomes (via the generation of nicotinic acid‚Äďadenine dinucleotide phosphate, NAADP), may also be involved. Although this is a contested area this description summarizes the essentials of the ‚Äėcanonical‚Äô pathway for glucose-stimulated insulin secretion. |
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Formal Description Interaction-ID: 54550 |
drug/chemical compound decreases_activity of complex/PPI ATP-sensitive potassium channel complex |
| Comment | Central to glucose sensing by beta-cells is the stimulation of glycolytic and oxidative metabolism of the sugar, ultimately causing enhanced mitochondrial ATP synthesis. Thus, flux through alternative pathways including the pentose phosphate shunt is usually small, though it may be increased under some circumstances. Increases in total, as well as free cytosolic mitochondrial matrix and sub-plasma membrane ATP/ADP ratios then lead to the closure of ATP-sensitive K + (KATP ) channels. The unbalanced influx of positively charged ions, notably Na + , then leads to plasma membrane depolarization, the firing of action potentials and the opening of voltage-gated Ca2 + channels. This, in turn, prompts the activation of secretory granule-associated small N- ethylmaleimide-sensitive factor receptor (SNARE) proteins and granule fusion with the plasma membrane. Highly localized changes in free Ca2 +, for example at the inner surface of the plasma membrane, at the mouth of voltage-gated calcium channels, and at the surface of secretory granules, are also believed to be important in controlling this process. Calcium release from intracellular organelles including the ER (endoplasmic reticulum) and Golgi [mediated via IP3 (inositol 1,4,5-trisphosphate)] as well as secretory granules and other acidic stores including lysosomes (via the generation of nicotinic acid‚Äďadenine dinucleotide phosphate, NAADP), may also be involved. Although this is a contested area this description summarizes the essentials of the ‚Äėcanonical‚Äô pathway for glucose-stimulated insulin secretion. |
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Formal Description Interaction-ID: 54551 |
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| Comment | Central to glucose sensing by beta-cells is the stimulation of glycolytic and oxidative metabolism of the sugar, ultimately causing enhanced mitochondrial ATP synthesis. Thus, flux through alternative pathways including the pentose phosphate shunt is usually small, though it may be increased under some circumstances. Increases in total, as well as free cytosolic mitochondrial matrix and sub-plasma membrane ATP/ADP ratios then lead to the closure of ATP-sensitive K + (KATP ) channels. The unbalanced influx of positively charged ions, notably Na + , then leads to plasma membrane depolarization, the firing of action potentials and the opening of voltage-gated Ca2 + channels. This, in turn, prompts the activation of secretory granule-associated small N- ethylmaleimide-sensitive factor receptor (SNARE) proteins and granule fusion with the plasma membrane. Highly localized changes in free Ca2 +, for example at the inner surface of the plasma membrane, at the mouth of voltage-gated calcium channels, and at the surface of secretory granules, are also believed to be important in controlling this process. Calcium release from intracellular organelles including the ER (endoplasmic reticulum) and Golgi [mediated via IP3 (inositol 1,4,5-trisphosphate)] as well as secretory granules and other acidic stores including lysosomes (via the generation of nicotinic acid‚Äďadenine dinucleotide phosphate, NAADP), may also be involved. Although this is a contested area this description summarizes the essentials of the ‚Äėcanonical‚Äô pathway for glucose-stimulated insulin secretion. |
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Formal Description Interaction-ID: 54552 |
drug/chemical compound increases_activity of complex/PPI Voltage-gated calcium channel |
| Comment | Central to glucose sensing by beta-cells is the stimulation of glycolytic and oxidative metabolism of the sugar, ultimately causing enhanced mitochondrial ATP synthesis. Thus, flux through alternative pathways including the pentose phosphate shunt is usually small, though it may be increased under some circumstances. Increases in total, as well as free cytosolic mitochondrial matrix and sub-plasma membrane ATP/ADP ratios then lead to the closure of ATP-sensitive K + (KATP ) channels. The unbalanced influx of positively charged ions, notably Na + , then leads to plasma membrane depolarization, the firing of action potentials and the opening of voltage-gated Ca2 + channels. This, in turn, prompts the activation of secretory granule-associated small N- ethylmaleimide-sensitive factor receptor (SNARE) proteins and granule fusion with the plasma membrane. Highly localized changes in free Ca2 +, for example at the inner surface of the plasma membrane, at the mouth of voltage-gated calcium channels, and at the surface of secretory granules, are also believed to be important in controlling this process. Calcium release from intracellular organelles including the ER (endoplasmic reticulum) and Golgi [mediated via IP3 (inositol 1,4,5-trisphosphate)] as well as secretory granules and other acidic stores including lysosomes (via the generation of nicotinic acid‚Äďadenine dinucleotide phosphate, NAADP), may also be involved. Although this is a contested area this description summarizes the essentials of the ‚Äėcanonical‚Äô pathway for glucose-stimulated insulin secretion. |
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Formal Description Interaction-ID: 54554 |
complex/PPI Voltage-gated calcium channel increases_activity of process |
| Comment | Besides glucose, a range of other fuel secretagogues including amino acids such as leucine, and the alpha-ketoacid ketoisocaproate are also ‚Äėprimary‚Äô metabolic stimulators of insulin release, and are likely, at least in part, to engage the same metabolic signalling pathways activated by glucose. |
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Formal Description Interaction-ID: 54555 |
drug/chemical compound increases_activity of process |
| Comment | Besides glucose, a range of other fuel secretagogues including amino acids such as leucine, and the alpha-ketoacid ketoisocaproate are also ‚Äėprimary‚Äô metabolic stimulators of insulin release, and are likely, at least in part, to engage the same metabolic signalling pathways activated by glucose. |
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Formal Description Interaction-ID: 54556 |
drug/chemical compound increases_activity of process |
| Comment | Forming a distinct group from the above, a range of physiologically-important secretory ‚Äėpotentiators‚Äô also exists. These enhance insulin release only at permissive (i.e. stimulatory; usually above 6 mM) glucose concentrations. The latter group includes the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP), as well as cholesystokinin (CCK), peptide YY (PYY) and oxyntomodulin, released from the gut in response to food transit. These are responsible for the augmentation of insulin release in response to food intake versus an identical change in glycemia imposed by intravenous injection of the sugar. |
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Formal Description Interaction-ID: 54557 |
gene/protein increases_activity of process |
| Comment | Forming a distinct group from the above, a range of physiologically-important secretory ‚Äėpotentiators‚Äô also exists. These enhance insulin release only at permissive (i.e. stimulatory; usually above 6 mM) glucose concentrations. The latter group includes the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP), as well as cholesystokinin (CCK), peptide YY (PYY) and oxyntomodulin, released from the gut in response to food transit. These are responsible for the augmentation of insulin release in response to food intake versus an identical change in glycemia imposed by intravenous injection of the sugar. |
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Formal Description Interaction-ID: 54558 |
gene/protein increases_activity of process |
| Comment | Forming a distinct group from the above, a range of physiologically-important secretory ‚Äėpotentiators‚Äô also exists. These enhance insulin release only at permissive (i.e. stimulatory; usually above 6 mM) glucose concentrations. The latter group includes the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP), as well as cholesystokinin (CCK), peptide YY (PYY) and oxyntomodulin, released from the gut in response to food transit. These are responsible for the augmentation of insulin release in response to food intake versus an identical change in glycemia imposed by intravenous injection of the sugar. |
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Formal Description Interaction-ID: 54559 |
gene/protein increases_activity of process |
| Comment | Forming a distinct group from the above, a range of physiologically-important secretory ‚Äėpotentiators‚Äô also exists. These enhance insulin release only at permissive (i.e. stimulatory; usually above 6 mM) glucose concentrations. The latter group includes the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP), as well as cholesystokinin (CCK), peptide YY (PYY) and oxyntomodulin, released from the gut in response to food transit. These are responsible for the augmentation of insulin release in response to food intake versus an identical change in glycemia imposed by intravenous injection of the sugar. |
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Formal Description Interaction-ID: 54560 |
gene/protein increases_activity of process |
| Comment | Forming a distinct group from the above, a range of physiologically-important secretory ‚Äėpotentiators‚Äô also exists. These enhance insulin release only at permissive (i.e. stimulatory; usually above 6 mM) glucose concentrations. The latter group includes the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP), as well as cholesystokinin (CCK), peptide YY (PYY) and oxyntomodulin, released from the gut in response to food transit. These are responsible for the augmentation of insulin release in response to food intake versus an identical change in glycemia imposed by intravenous injection of the sugar. |
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Formal Description Interaction-ID: 54561 |
gene/protein increases_activity of process |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54562 |
gene/protein increases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for GLP1R |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54563 |
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| Drugbank entries | Show/Hide entries for GLP1R or cAMP |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54564 |
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| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54565 |
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| Drugbank entries | Show/Hide entries for cAMP |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54566 |
drug/chemical compound increases_activity of complex/PPI Protein kinase A |
| Drugbank entries | Show/Hide entries for cAMP |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54567 |
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| Drugbank entries | Show/Hide entries for cAMP |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54568 |
drug/chemical compound increases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for Acetylcholine or CHRM3 |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54569 |
drug/chemical compound increases_activity of complex/PPI P2X purinoreceptor |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54570 |
drug/chemical compound increases_activity of complex/PPI P2Y purinoreceptor |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54571 |
drug/chemical compound increases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for FFAR1 |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54572 |
gene/protein increases_quantity of drug/chemical compound |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54574 |
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| Drugbank entries | Show/Hide entries for CHRM3 |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54575 |
complex/PPI P2X purinoreceptor increases_quantity of drug/chemical compound |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54576 |
complex/PPI P2Y purinoreceptor increases_quantity of drug/chemical compound |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54577 |
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| Drugbank entries | Show/Hide entries for FFAR1 |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54578 |
drug/chemical compound increases_activity of process |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54579 |
drug/chemical compound increases_activity of process |
| Drugbank entries | Show/Hide entries for cAMP |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54580 |
gene/protein increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for cAMP |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54581 |
gene/protein increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for cAMP |
| Comment | The incretins act via specific G [Gs ] protein-coupled receptors (GPCRs, e.g. GLP1R and GIPR) on the beta-cell surface to increase intracellular cAMP concentrations, activating protein kinase A (PKA), as well as exchange protein activated by cAMP 2 (EPAC2) and other signalling pathways (mediated, for example, by beta arrestin and MAPK). Acetyl-choline, acting through muscarinic M3 receptors, and ATP (via P2X and P2Y purinoreceptors), as well as fatty acids (via GPR40/FFAR1), and vasopressin, also enhance secretion triggered by nutrients by increasing cytosolic Ca2 + , whereas vasoactive intestinal peptide (VIP), PYY and oxyntomodulin probably act via cAMP. |
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Formal Description Interaction-ID: 54582 |
gene/protein increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for cAMP |
| Comment | Inhibitors of secretion include somatostatin, which acts in part via an inhibitory G protein, adrenaline (epinephrine) and noradrenaline (norepinephrine), the latter acting through alpha2 receptors to open KATP channels and hyperpolarize the cell. The actions of epinephrine (and norepinephrine) are important to suppress insulin release during exercise. |
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Formal Description Interaction-ID: 54583 |
gene/protein decreases_activity of process |
| Comment | Inhibitors of secretion include somatostatin, which acts in part via an inhibitory G protein, adrenaline (epinephrine) and noradrenaline (norepinephrine), the latter acting through alpha2 receptors to open KATP channels and hyperpolarize the cell. The actions of epinephrine (and norepinephrine) are important to suppress insulin release during exercise. |
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Formal Description Interaction-ID: 54584 |
drug/chemical compound decreases_activity of process |
| Comment | Inhibitors of secretion include somatostatin, which acts in part via an inhibitory G protein, adrenaline (epinephrine) and noradrenaline (norepinephrine), the latter acting through alpha2 receptors to open KATP channels and hyperpolarize the cell. The actions of epinephrine (and norepinephrine) are important to suppress insulin release during exercise. |
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Formal Description Interaction-ID: 54585 |
drug/chemical compound decreases_activity of process |
| Comment | Fructose appears to be able to prompt insulin secretion in vitro and in vivo via the sweet taste receptor T1R2, an effect which may potentiate the effects of glucose. |
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Formal Description Interaction-ID: 54586 |
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| Drugbank entries | Show/Hide entries for Fructose or TAS1R2 |
| Comment | Fructose appears to be able to prompt insulin secretion in vitro and in vivo via the sweet taste receptor T1R2, an effect which may potentiate the effects of glucose. |
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Formal Description Interaction-ID: 54587 |
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| Drugbank entries | Show/Hide entries for TAS1R2 |
| Comment | The identification in islets of a high Michaelis constant, and cooperative HK (hexokinase) type IV, GK (glucokinase), encoded by GCK, present alongside higher affinity hexokinases, suggests that glucose phosphorylation is the key flux-generating step. Subsequent studies revealed that the higher affinity HKs are largely absent from highly purified beta-cells. Importantly, and providing direct evidence for the importance of GK in controlling insulin secretion in man, mutations in the human GCK gene lead to monogenic diabetes (maturity onset diabetes of the young-2; MODY2). |
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Formal Description Interaction-ID: 54588 |
gene/protein increases_activity of process |
| Drugbank entries | Show/Hide entries for GCK |
| Comment | Demonstrating the importance of mitochondrial metabolism in the regulation of insulin secretion in man, abnormalities in the expression of the mitochondrial genome are associated with impaired insulin secretion in maternally-inherited diabetes and deafness (tRNALeu mutation). Likewise, T2D-associated variants in the human transcription factor B1 mitochondria (TFB1M) gene lead to impaired mitochondrial oxidative phosphorylation. |
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Formal Description Interaction-ID: 54589 |
phenotype affects_activity of process |
| Comment | Demonstrating the importance of mitochondrial metabolism in the regulation of insulin secretion in man, abnormalities in the expression of the mitochondrial genome are associated with impaired insulin secretion in maternally-inherited diabetes and deafness (tRNALeu mutation). Likewise, T2D-associated variants in the human transcription factor B1 mitochondria (TFB1M) gene lead to impaired mitochondrial oxidative phosphorylation. |
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Formal Description Interaction-ID: 54590 |
gene/protein mutant increases_activity of |
| Comment | Demonstrating the importance of mitochondrial metabolism in the regulation of insulin secretion in man, abnormalities in the expression of the mitochondrial genome are associated with impaired insulin secretion in maternally-inherited diabetes and deafness (tRNALeu mutation). Likewise, T2D-associated variants in the human transcription factor B1 mitochondria (TFB1M) gene lead to impaired mitochondrial oxidative phosphorylation. |
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Formal Description Interaction-ID: 54591 |
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| Comment | Demonstrating the importance of mitochondrial metabolism in the regulation of insulin secretion in man, abnormalities in the expression of the mitochondrial genome are associated with impaired insulin secretion in maternally-inherited diabetes and deafness (tRNALeu mutation). Likewise, T2D-associated variants in the human transcription factor B1 mitochondria (TFB1M) gene lead to impaired mitochondrial oxidative phosphorylation. |
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Formal Description Interaction-ID: 54592 |
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| Comment | The cell permeant mitochondrial substrates methylsuccinate and methylpyruvate are potent stimulators of insulin secretion in both rodent and human islets. |
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Formal Description Interaction-ID: 54593 |
drug/chemical compound Methylsuccinic acid increases_activity of process |
| Comment | The cell permeant mitochondrial substrates methylsuccinate and methylpyruvate are potent stimulators of insulin secretion in both rodent and human islets. |
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Formal Description Interaction-ID: 54594 |
drug/chemical compound increases_activity of process |