INSULIN SECRETION PATHWAY (PW:0000674)

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Description

In response to elevated blood glucose, the pancreatic beta cells of the islets of Langerhans secrete insulin. Processed insulin is stored in secretory granules along with other low molecular weight molecules and metals. Glucose levels couple to changes in membrane potential to regulate secretion of insulin-granules. Beta cells express a high capacity glucose transporter and the G6P insensitive glucokinase. Fast uptake of glucose into the cell and rapid phosphorylation are followed by its

Pathway Diagram:

Elsevier Inc. Cdc42 Rab27a Slc2a2 Gck NADPH ATP ATP biosynthetic pathway electron transport chain pathway oxidative phosphorylation pathway citric acid cycle pathway pyruvate metabolic pathway Snap25 ---| voltage-gated K+ channels membrane repolarization ---| voltage-gated Ca2+ channels membrane depolarization --+> voltage-gated Ca2+ channels Ca2+ glucose-6-P D-glucose elevated glucose levels elevated glucose levels ---> D-glucose Snap25 ---- voltage-gated K+ channels Munc proteins ---> Stx1a pyruvate  cycling D-glucose ---> glucose-6-P glucose-6-P ---> glycolysis pathway membrane repolarization voltage-gated Ca2+ channels ---> Ca2+ insulin released citric acid cycle pathway ---> pyruvate  cycling membrane depolarization ATP-sensitive K+ channels ---> membrane depolarization voltage-gated K+ channels ---> membrane repolarization Rab family mediated signaling pathway Rho/Rac/Cdc42 mediated signaling pathway Snap25 Vamp2 Rab3a ATP-sensitive K+ channels voltage-gated Ca2+ channels voltage-gated K+ channels Syt proteins Munc proteins Stx1a membrane depolarization --+> voltage-gated K+ channels glycolysis pathway pyruvate metabolic pathway ---> pyruvate  cycling ATP ---> ATP-sensitive K+ channels
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Genes in Pathway:

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insulin secretion pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Abcc8 ATP binding cassette subfamily C member 8 JBrowse link 1 102,110,708 102,191,287 RGD:2311063
G Cacna1a calcium voltage-gated channel subunit alpha1 A JBrowse link 19 25,453,236 25,749,550 RGD:2311105
G Cacna1c calcium voltage-gated channel subunit alpha1 C JBrowse link 4 150,635,808 151,270,790 RGD:2311105
G Cacna1d calcium voltage-gated channel subunit alpha1 D JBrowse link 16 6,110,294 6,405,022 RGD:2311105
G Cdc42 cell division cycle 42 JBrowse link 5 155,690,267 155,728,385 RGD:2311087
G Gck glucokinase JBrowse link 14 86,149,146 86,191,589 RGD:2311061
G Kcnb1 potassium voltage-gated channel subfamily B member 1 JBrowse link 3 163,850,785 163,935,610 RGD:2311121
G Kcnj11 potassium voltage-gated channel subfamily J member 11 JBrowse link 1 102,103,093 102,107,134 RGD:2311063
G Rab27a RAB27A, member RAS oncogene family JBrowse link 8 79,722,334 79,776,228 RGD:2311087
G Rab3a RAB3A, member RAS oncogene family JBrowse link 16 20,435,098 20,439,206 RGD:2311087
G Slc2a2 solute carrier family 2 member 2 JBrowse link 2 114,413,427 114,445,418 RGD:2311061
G Snap25 synaptosomal-associated protein 25 JBrowse link 3 129,697,408 129,788,417 RGD:2311121
G Stx1a syntaxin 1A JBrowse link 12 24,682,050 24,710,002 RGD:2311087
G Stxbp1 syntaxin binding protein 1 JBrowse link 3 11,823,779 11,885,479 RGD:2311087
G Syt7 synaptotagmin 7 JBrowse link 1 226,435,816 226,498,008 RGD:2311143
RGD:2311148
G Syt7_v1 synaptotagmin 7, variant 1 RGD:2311143
G Syt9 synaptotagmin 9 JBrowse link 1 171,592,703 171,769,780 RGD:2311147
RGD:2311148
G Unc13a unc-13 homolog A JBrowse link 16 20,056,398 20,103,951 RGD:2311087
G Vamp2 vesicle-associated membrane protein 2 JBrowse link 10 55,675,171 55,679,405 RGD:2311087
altered insulin secretion pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Abcc8 ATP binding cassette subfamily C member 8 JBrowse link 1 102,110,708 102,191,287 RGD:2313628
G Kcnj11 potassium voltage-gated channel subfamily J member 11 JBrowse link 1 102,103,093 102,107,134 RGD:2313610
RGD:2313628

Altered Pathway:

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Gene GroupMuncsaccessory factors
Functional ClassKATPATP-sensitive potassium channels
Functional ClassSytssynaptotagmin family of calcium-binding proteins
Functional ClassVDCCvoltage-gated calcium channels
Functional ClassKcnvoltage-gated potassium channels

Pathway Gene Annotations

Disease Annotations Associated with Genes in the insulin secretion pathway
Disease TermsGene Symbols
Abnormalities, MultipleCacna1c , Cdc42 , Snap25 , Stxbp1
AdenomaCacna1d
Adrenal Gland NeoplasmsCdc42
Alzheimer DiseaseCdc42
Amyotrophic Lateral SclerosisUnc13a
Arrhythmias, CardiacCacna1c
Arthritis, ExperimentalCdc42
AtaxiaCacna1a
Autism Spectrum DisorderStx1a
Autistic DisorderCacna1c , Stx1a
Bipolar DisorderCacna1c , Cdc42 , Snap25
Brain EdemaAbcc8
Brain InjuriesAbcc8
Breast NeoplasmsSlc2a2
Brugada SyndromeCacna1c
Brugada Syndrome 3Cacna1c
CarcinomaCdc42
Carcinoma, Ductal, BreastCacna1c
Carcinoma, HepatocellularSlc2a2
Carcinoma, Pancreatic DuctalSlc2a2
Cardiac Complexes, PrematureCacna1c
Cardiomyopathy, RestrictiveCacna1c
Colorectal NeoplasmsAbcc8
Congenital AbnormalitiesRab27a
Congenital HyperinsulinismAbcc8 , Gck , Kcnj11
Coronary Artery DiseaseGck
Creutzfeldt-Jakob SyndromeStx1a
DeafnessCacna1d
Death, Sudden, CardiacCacna1c
Depressive DisorderSnap25
Developmental DisabilitiesCacna1a
Diabetes MellitusAbcc8 , Gck , Kcnj11
Diabetes Mellitus, ExperimentalGck , Kcnj11 , Slc2a2 , Snap25
Diabetes Mellitus, Permanent NeonatalAbcc8 , Gck , Kcnj11
Diabetes Mellitus, Permanent Neonatal, with Neurologic FeaturesAbcc8 , Kcnj11
Diabetes Mellitus, Transient Neonatal, 2Abcc8
Diabetes Mellitus, Transient Neonatal, 3Kcnj11
Diabetes Mellitus, Type 1Abcc8 , Kcnj11
Diabetes Mellitus, Type 2Abcc8 , Gck , Kcnj11 , Slc2a2 , Snap25
Diabetes, GestationalGck
Down SyndromeSnap25
DysarthriaCacna1a
Dyskinesia, Drug-InducedCacna1d
EndotoxemiaAbcc8
EpendymomaRab3a
Epilepsies, MyoclonicStxbp1
EpilepsyCacna1c
Epilepsy, AbsenceCacna1a
Epilepsy, GeneralizedCacna1a , Stxbp1
Epilepsy, Temporal LobeCacna1a , Cdc42
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 26Kcnb1
Epileptic Encephalopathy, Early Infantile, 4Stxbp1
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 42Cacna1a
Episodic Ataxia with NystagmusCacna1a
Exfoliation SyndromeCacna1a
Fanconi SyndromeSlc2a2
Fatty LiverGck , Slc2a2
Fetal Growth RetardationUnc13a
FibrosarcomaCdc42
GastrinomaSlc2a2
Genetic Diseases, InbornCacna1a , Cacna1c , Cdc42 , Snap25 , Stxbp1
GlucagonomaSlc2a2
Glycogen Storage DiseaseSlc2a2
Griscelli SyndromeRab27a
Griscelli Syndrome Type 2Rab27a
Heart ArrestAbcc8
Hemiplegic Migraine, Familial Type 1Cacna1a
Hernia, DiaphragmaticKcnb1
Hirschsprung DiseaseStx1a
Histiocytosis, Non-Langerhans-CellRab27a
HIV InfectionsCdc42
HyperaldosteronismCacna1d
HyperglycemiaGck
Hyperinsulinemic Hypoglycemia, Familial, 3Gck
HyperinsulinismAbcc8 , Gck , Kcnj11
HyperplasiaAbcc8
HypertensionAbcc8 , Cacna1c , Gck , Kcnj11
Hypertrophy, Left VentricularKcnj11
HypoglycemiaAbcc8 , Cacna1c , Gck , Kcnj11
Hypoglycemia, Leucine-InducedAbcc8
HypopigmentationRab27a
Immunologic Deficiency SyndromesCacna1c
Infarction, Middle Cerebral ArteryAbcc8
Insulin ResistanceGck , Kcnj11
InsulinomaSlc2a2
Kidney Reperfusion InjuryKcnj11
Limb Deformities, CongenitalCacna1c
Liver Cirrhosis, ExperimentalGck
Liver InjuryGck
Long QT SyndromeCacna1c
Mammary Neoplasms, AnimalCdc42
Mammary Neoplasms, ExperimentalCdc42
Maturity-Onset Diabetes of the YoungAbcc8 , Gck , Kcnj11
Maturity-Onset Diabetes of the Young, Type 13Kcnj11
Maturity-Onset Diabetes of the Young, Type 2Gck , Kcnj11
MelanomaCacna1c
Melanoma, Cutaneous Malignant, Susceptibility To, 1Cacna1c
Memory DisordersCacna1d
Migraine DisordersCacna1a
Migraine with AuraCacna1a
Migraine, Sporadic HemiplegicCacna1a
MYASTHENIC SYNDROME, CONGENITAL, 18Snap25
Myocardial IschemiaKcnj11
Myocardial Reperfusion InjuryAbcc8 , Kcnj11
NecrosisAbcc8 , Cdc42
NesidioblastosisKcnj11
Neural Tube DefectsSlc2a2
Neuromuscular ManifestationsSnap25
ObesityGck
Parkinsonian DisordersAbcc8 , Kcnj11
Paroxysmal ventricular fibrillationCacna1c
Prediabetic StateKcnj11
PresbycusisCacna1d
Primary Aldosteronism, Seizures, and Neurologic AbnormalitiesCacna1d
Prostatic NeoplasmsCacna1d , Stxbp1
Psychotic DisordersSnap25
Reperfusion InjuryCdc42
RhinitisCdc42
SchizophreniaCacna1c
Sciatic NeuropathyAbcc8 , Cacna1d , Kcnj11
SeizuresAbcc8 , Cacna1a , Kcnj11
Short Qt SyndromeCacna1c
Sinoatrial Node Dysfunction and DeafnessCacna1d
Spasms, InfantileStxbp1
Spinal Cord InjuriesAbcc8 , Cdc42
Spinocerebellar AtaxiasCacna1a
Status EpilepticusAbcc8 , Kcnj11
StrokeAbcc8
Subarachnoid HemorrhageAbcc8
Subarachnoid Hemorrhage, TraumaticAbcc8
Tachycardia, VentricularCacna1c
Takenouchi-Kosaki SyndromeCdc42
TicsSnap25
Timothy SyndromeCacna1c
Ventricular Fibrillation, Paroxysmal Familial, 1Cacna1c
X-Linked Infantile Spasm SyndromeStxbp1
Pathway Annotations Associated with Genes in the insulin secretion pathway
Pathway TermsGene Symbols
acebutolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
adenosine signaling pathwayCdc42
adrenergic beta receptor agonist and beta-blocker pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
alfentanil pharmacodynamics pathwayCacna1a
altered insulin secretion pathwayAbcc8 , Kcnj11
Alzheimer disease pathwayCacna1c , Cacna1d
amino sugar metabolic pathwayGck
amiodarone pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
amlodipine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
arrhythmogenic right ventricular cardiomyopathy pathwayCacna1c , Cacna1d
atenolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
betaxolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
bisoprolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
bupivacaine pharmacodynamics pathwayCacna1a
bupranolol drug pathwayAbcc8 , Cacna1c , Kcnj11
bupranolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
buprenorphine pharmacodynamics pathwayCacna1a
butirosin and neomycin biosynthetic pathwayGck
c-Jun N-terminal kinases MAPK signaling pathwayCdc42
calcium transport pathwayCacna1a , Cacna1c , Cacna1d
calcium/calcium-mediated signaling pathwayCacna1a , Cacna1c , Cacna1d , Syt7 , Syt9
calcium/calmodulin dependent kinase 2 signaling pathwayCacna1c
carvedilol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
ceramide signaling pathwayCdc42
chemokine mediated signaling pathwayCdc42
chloroprocaine pharmacodynamics pathwayCacna1a
citalopram pharmacodynamics pathwayCacna1a
cocaine pharmacodynamics pathwayCacna1a
codeine and morphine pharmacodynamics pathwayCacna1a
desipramine pharmacodynamics pathwayCacna1a
diabetes pathwayAbcc8
dilated cardiomyopathy pathwayCacna1c , Cacna1d
diltiazem pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
diphenoxylate pharmacodynamics pathwayCacna1a
disopyramide pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
dobutamine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
E-cadherin signaling pathwayCdc42
endocytosis pathwayCdc42
endothelin signaling pathwayCdc42
ephrin - ephrin receptor bidirectional signaling axisCdc42
escitalopram pharmacodynamics pathwayCacna1a
esmolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
ethylmorphine pharmacodynamics pathwayCacna1a
facilitative sugar transporter mediated glucose transport pathwaySlc2a2
fanconi syndrome pathwaySlc2a2
Fc gamma receptor mediated signaling pathwayCdc42
felodipine pharmacokinetics pathwayCacna1c
fentanyl pharmacodynamics pathwayCacna1a
flecainde pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
fluoxetine pharmacodynamics pathwayCacna1a
forkhead class A signaling pathwayAbcc8 , Gck , Kcnj11 , Slc2a2
fosphenytoin pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
fructose-1,6-diphosphatase deficiency pathwaySlc2a2
galactose metabolic pathwayGck
GALE deficiency pathwayGck
GALK deficiency pathwayGck
GALT deficiency pathwayGck
gliclazide pharmacodynamics pathwayAbcc8 , Cacna1a , Slc2a2
gluconeogenesis pathwayGck , Slc2a2
glutamate signaling pathwayCacna1a , Cacna1c , Cacna1d
glyburide pharmacodynamics pathwayAbcc8 , Cacna1a , Slc2a2
glycogen biosynthetic pathwayGck
glycogen metabolic pathwayGck
glycogen storage disease pathway, type IASlc2a2
glycogen storage disease pathway, type IBSlc2a2
glycogen storage disease pathway, type IIIGck
glycogen storage disease pathway, type IV.Gck
glycogen storage disease pathway, type VIGck
glycogen storage disease pathway, type VIISlc2a2
glycolysis pathwayGck , Slc2a2
glycolysis/gluconeogenesis pathwayGck
gonadotropin-releasing hormone signaling pathwayCacna1c , Cacna1d , Cdc42
heroin pharmacodynamics pathwayCacna1a
hydrocodone pharmacodynamics pathwayCacna1a
hydromorphone pharmacodynamics pathwayCacna1a
hypertrophic cardiomyopathy pathwayCacna1c , Cacna1d
hypoxia inducible factor pathwayGck
ibutilide pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
imipramine pharmacodynamics pathwayCacna1a
insulin responsive facilitative sugar transporter mediated glucose transport pathwayVamp2
insulin secretion pathwayAbcc8 , Cacna1a , Cacna1c , Cacna1d , Cdc42 , Gck , Kcnb1 , Kcnj11 , Rab27a , Rab3a , Slc2a2 , Snap25 , Stx1a , Stxbp1 , Syt7 , Syt7_v1 , Syt9 , Unc13a , Vamp2
insulin signaling pathwayGck
isoprenaline pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
isradipine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
lactose degradation pathwaySlc2a2
levacetylmethadol pharmacodynamics pathwayCacna1a
levobunolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
levobupivacaine phgarmacodynamics pathwayCacna1a
levorphanol pharmacodynamics pathwayCacna1a
lidocaine pharmacodynamics pathwayAbcc8 , Cacna1a , Cacna1c , Kcnj11
long term depressionCacna1a
long term potentiationCacna1c
maturity onset diabetes of the young pathwayGck , Slc2a2
mepivacaine pharmacodynamics pathwayCacna1a
methadone pharmacodynamics pathwayCacna1a
metoprolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
mexiletine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
mitogen activated protein kinase signaling pathwayCacna1a , Cacna1c , Cacna1d , Cdc42
N-cadherin signaling pathwayCdc42
nadolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
nalbuphine pharmacodynamics pathwayCacna1a
naloxone pharmacodynamics pathwayCacna1a
naltrexone pharmacodynamics pathwayCacna1a
nebivolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
neurotrophic factor signaling pathwayCdc42
nicotine pharmacodynamics pathwayCacna1a
nifedipine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
nimodipine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
nisoldipine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
nitrendipine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
nucleotide sugar metabolic pathwayGck
oxybuprocaine pharmacodynamics pathwayCacna1a
oxycodone pharmacodynamics pathwayCacna1a
oxymorphone pharmacodynamics pathwayCacna1a
p38 MAPK signaling pathwayCdc42
pancreatic cancer pathwayCdc42
penbutolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
pentazocine pharmacodynamics pathwayCacna1a
phenytoin pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
phosphoenolpyruvate carboxykinase deficiency pathwaySlc2a2
pindolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
potassium channel inhibitors pharmacodynamics pathwayAbcc8 , Cacna1a , Slc2a2
prilocaine pharmacodynamics pathwayCacna1a
procainamide pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
procaine pharmacodynamics pathwayCacna1a
propranolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
quinidine pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
remifentanil pharmacodynamics pathwayCacna1a
renal cell cancer pathwayCdc42
Rho/Rac/Cdc42 mediated signaling pathwayCdc42
ropivacaine pharmacodynamics pathwayCacna1a
sotalol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
sphingosine 1-phosphate signaling pathwayCdc42
starch and sucrose metabolic pathwayGck
Sucrase-isomaltase deficiency pathwayGck
synaptic vesicle exocytosis - neurotransmitter release pathwayStxbp1
T cell receptor signaling pathwayCdc42
timolol pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
tramadol pharmacodynamics pathwayCacna1a
trehalose degradation pathwayGck , Slc2a2
triosephosphate isomerase deficiency pathwaySlc2a2
type 2 diabetes mellitus pathwayAbcc8 , Cacna1a , Cacna1c , Cacna1d , Gck , Kcnj11 , Slc2a2
vascular endothelial growth factor signaling pathwayCdc42
vasopressin signaling pathwayVamp2
vasopressin signaling pathway via receptor type 2Vamp2
verapamil pharmacodynamics pathwayAbcc8 , Cacna1c , Kcnj11
Wnt signaling, non-canonical pathwayCdc42
Phenotype Annotations Associated with Genes in the insulin secretion pathway

References Associated with the insulin secretion pathway:

Ontology Path Diagram:

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